Association between Levels of Serum Ferritin and Bone Mineral Density in Korean Premenopausal and Postmenopausal Women: KNHANES 2008–2010

Background

As women go through menopause, serum estrogen decreases and ferritin increases. Decreased serum estrogen is well known to cause detrimental effects on bone health; however, data on the associations of serum ferritin with BMD before and after menopause are still lacking. Therefore, this study aimed to investigate the association between serum ferritin levels and BMD in premenopausal and postmenopausal Korean women.

Methods

This study was performed using data from the 2008–2010 Korean National Health and Nutrition Examination Survey, including 7300 women (4229 premenopausal and 3071 postmenopausal). BMD was measured using dual X-ray absorptiometry at the femur and the lumbar spine, and serum ferritin levels were measured by chemiluminescent immunoassay.

Results

Median serum ferritin levels in postmenopausal women were higher than those in premenopausal women despite the same age ranges. Serum ferritin levels were only significantly correlated with BMD on the lumbar spine (β = −0.189, p-value = 0.005) in premenopausal women after adjusting confounding factors. Additionally, BMD on the lumbar spine had tended to decrease as serum ferritin quartiles increase (P for trend = 0.035) in premenopausal women after adjusting confounding factors. On the other hand, there were no significant associations between serum ferritin levels and BMD on the total femur and, femur neck in premenopausal women, and BMD on the total femur, femur neck, and lumbar spine in postmenopausal women.

Conclusion

Increased serum ferritin levels were significantly associated with BMD in premenopausal women, particularly on the lumbar spine, but not in postmenopausal women.     

Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan

Background

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.

Methods

We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.

Results

Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H₂-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.

Conclusions

The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.     

A New Polymorphism Biomarker rs629367 Associated with Increased Risk and Poor Survival of Gastric Cancer in Chinese by Up-Regulated miRNA-let-7a Expression

Background

Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms.

Methods

A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing.

Results

We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001).

Conclusions

pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.     

MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

Background

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.

Methodology/Principal Findings

We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression.

Conclusions/Significance

Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.     

Association between Depressive Symptoms and Bone Stiffness Index in Young Adults: The Kangwha Study

Objective

Young adulthood is an important period for both bone and mental health. This study investigated the association between depressive symptoms and bone density in apparently healthy Korean men and women aged 29−32 years.

Methods

This study is a cross-sectional analysis of data from 123 men and 133 women who completed follow-up examinations of the Kangwha study in 2010−2011. Bone stiffness index (SI) was measured at the os calcis using a quantitative ultrasound device. Depressive symptoms were evaluated using the Korean version of the Beck Depression Inventory (K-BDI) and classified as normal (K-BDI <10), mild (K-BDI 10–15), and moderate to severe (K-BDI ≥16).

Results

Moderate to severe depressive symptoms were prevalent among 11.4% of men and 19.6% of women. Higher K-BDI scores were significantly correlated to SI in men, before (ρ = –0.286, p = 0.001) and after (ρ = –0.228, p = 0.013) adjustment for covariates. Men with depressive symptoms tended to have a lower SI; multivariate-adjusted mean SI in men with normal, mild, and moderate to severe depressive symptoms was 104.1±3.1, 100.9±5.9, and 94.1±7.8, respectively (p for trend = 0.021). In contrast, no significant correlations were identified in women.

Conclusions

Depressive symptoms were significantly associated with lower SI in men, but not in women. Further studies are necessary to evaluate the impact of depression on developing osteoporosis or osteoporotic fractures later in life.     

Educational Level,Obesity and Incidence of Diabetes among Chinese Adult Men and Women Aged 18–59 Years Old: An 11-Year Follow-Up Study

Objective

To determine whether educational level and overweight/obesity was associated with the development of diabetes among Chinese adult men and women.

Methods

A cohort (2000–2011) of 10 704 participants aged 18–59 years (8 238 men, 2 466 women) in Qingdao Port Health Study (QPHS) were recruited in this study. The personal lifestyle, height, weight, waist circumference, resting heart rate, blood pressure, fasting blood glucose, total cholesterol, triglycerides and plasma uric acid were collected annually in a comprehensive health checkup program. Cox proportional hazards regression models were used to estimate the association of factors and incidence of diabetes.

Results

During 110 825 person-years of follow-up, 1 056 new onset cases (9.5 per 1 000 person-years) of diabetes were identified. With normal weight as reference, the multiple-adjusted hazard ratio (HR) (95%CI) of diabetes was 1.69(1.38–2.09) for overweight and 2.24(1.66–3.02) for obesity among men, which was 1.81(1.12–2.92) and 2.58(1.37–4.86) among women, respectively. Compared with the participants with high educational level, those with low educational level had a higher risk of diabetes (multiple-adjusted HR (95%CI): 1.43(1.11–1.86)) among men. The association was not found among women and the adjusted HR (95%CI) of diabetes was 1.56(0.89–2.76). The increased risks of low educational level were independent of mediators among men, through normal weight (P for trend = 0.0313) and overweight (P for trend = 0.0212) group but not obesity group (P for trend = 0.0957).

Conclusion

Baseline overweight/obesity was an independent risk factor for diabetes for both men and women. Low educational level was adversely associated with incidence of diabetes through normal weight, overweight and obesity groups, with the association being substantially attenuated by mediating factors only in the obesity group among men. The association was not found among women.     

Reproductive Factors and Non-Hodgkin Lymphoma Risk in the California Teachers Study

Background

Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.

Methodology/Principal Findings

Women in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype.

Conclusions

Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.     

The Relationship between Endogenous Androgens and Body Fat Distribution in Early and Late Postmenopausal Women

Objectives

To investigate the relationship between endogenous androgens and body fat distribution in early and late postmenopausal women.

Materials and Methods

We enrolled postmenopausal women consisting of an early group (≤5 years since menopause, n = 105) and a late group (≥10 years since menopause, n = 107). Each group was subdivided into normal weight (BMI <24 kg/m²) group, overweight and obese (BMI ≥24 kg/m²) group. Fasting total testosterone (T), dehydroepiandrosterone-sulfate (DHEA-S) and sex hormone-binding globulin (SHBG) levels were measured. Body fat distribution was evaluated by dual-energy X-ray absorptiometry (DEXA).

Results

Late postmenopausal women had a higher proportion of body fat than early postmenopausal women. The body fat of the overweight and obese women had a greater tendency to accumulate in the abdomen compared with the normal weight women both in early and late postmenopausal groups. The overweight and obese women had a higher free testosterone (FT) than the normal weight women in early postmenopausal women (P<0.05). In late postmenopausal women, the overweight and obese women had higher DHEA-S levels than normal weight women (P<0.05). No direct relationship was observed between the T levels and body fat distribution both in early and late postmenopausal groups (P>0.05).The FT in early postmenopausal women and the DHEA-S levels in late postmenopausal women correlated positively with the trunk/leg fat ratio (T/L) and the proportion of android fat whereas correlated negatively with the proportion of gynoid fat in the partial correlation and multiple linear regression analyses (all P<0.05).

Conclusions

Serum T levels do not correlate directly with body fat distribution, the FT in early postmenopausal women and DHEA-S levels in late postmenopausal women correlate positively with abdominal fat accumulation.     

Associations between Rice,Noodle, and Bread Intake and Sleep Quality in Japanese Men and Women

Background

Previous studies have shown that a diet with a high-glycemic index is associated with good sleep quality. Therefore, we investigated the association of sleep quality with the intake of 3 common starchy foods with different glycemic indexes–rice, bread, and noodles–as well as the dietary glycemic index in a Japanese population.

Methods

The participants were 1,848 men and women between 20 and 60 years of age. Rice, bread, and noodle consumption was evaluated using a self-administered diet history questionnaire. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index, and a global score >5.5 was considered to indicate poor sleep.

Results

Multivariate-adjusted odds ratios (95% confidence intervals) for poor sleep across the quintiles of rice consumption were 1.00 (reference), 0.68 (0.49–0.93), 0.61 (0.43–0.85), 0.59 (0.42–0.85), and 0.54 (0.37–0.81) (p for trend = 0.015); those for the quintiles of noodle consumption were 1.00 (reference), 1.25 (0.90–1.74), 1.05 (0.75–1.47), 1.31 (0.94–1.82), and 1.82 (1.31–2.51) (p for trend = 0.002). Bread intake was not associated with sleep quality. A higher dietary glycemic index was significantly associated with a lower risk of poor sleep (p for trend = 0.020).

Conclusion

A high dietary glycemic index and high rice consumption are significantly associated with good sleep in Japanese men and women, whereas bread intake is not associated with sleep quality and noodle consumption is associated with poor sleep. The different associations of these starchy foods with sleep quality might be attributable to the different glycemic index of each food.     

Overtime Work and Prevalence of Diabetes in Japanese Employees: Japan Epidemiology Collaboration on Occupational Health Study

Objective

Epidemiologic evidence on long working hour and diabetes has been conflicting. We examined the association between overtime work and prevalence of diabetes among Japanese workers.

Methods

The subjects were 40,861 employees (35,170 men and 5,691 women), aged 16 to 83 years, of 4 companies in Japan. Hours of overtime were assessed using self-reported questionnaires. Diabetes was defined as a fasting plasma glucose ≥126 mg/dl (7.0 mmol/l), hemoglobin A1c ≥6.5% (48 mmol/mol), or current use of anti-diabetic drug. Multiple logistic regression analysis was used to calculate odds ratio of diabetes for each category of overtime.

Results

After adjustment for age, sex, company, smoking, and BMI, there was a suggestion of U-shaped relationship between overtime work and prevalence of diabetes (P for quadratic trend = 0.07). Compared with those who worked <45 hours of overtime per month, the adjusted odds ratios (95% confidence interval) of diabetes were 0.86 (0.77–0.94), 0.69 (0.53–0.89), and 1.03 (0.72–1.46) for those who worked 45–79, 80–99, and ≥100 hours of overtime per month, respectively. In one company (n = 33,807), where other potential confounders including shift work, job position, type of department, alcohol consumption, sleep duration, leisure time physical activity, and family history of diabetes was additionally adjusted for, similar result was obtained (P for quadratic trend = 0.05).

Conclusions

Long hours of overtime work may not be associated with increased prevalence of diabetes among Japanese workers.     

The Associations of Serum Serotonin with Bone Traits Are Age- and Gender-Specific

Context

Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare.

Objective

The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men.

Subjects and Methods

Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay.

Results

Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = −0.22 to −0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = −0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits.

Conclusion

Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors.     

The Association between Aortic Calcification and Fracture Risk in Postmenopausal Women in China: The Prospective Chongqing Osteoporosis Study

Purpose

Fractures are associated with cardiovascular diseases in the elderly. The purpose of the present study was to investigate the association between aortic calcification (AC) and the risk of vertebral fractures in postmenopausal Chinese women.

Methods

A prospective study with 5 years of follow-up in 1724 postmenopausal women (aged 50 years old and older) was conducted from July 2005 to June 2010. Dual energy X-ray absorptiometry was utilized to evaluate bone mineral density (BMD). Aortic calcification score (ACS) was determined by a semi-quantitative method and was further categorized into four groups. Cox proportional hazards models were established to assess the association between AC and the risk of vertebral fractures.

Results

For subjects with AC, the incidence of vertebral fractures was higher than that of those without AC (p<0.01). After adjustment for age and other potential confounders, it was found that severe AC (G4, ACS>6; G3, ACS = 3–6) was associated with vertebral fractures. Severe AC (G4) was associated with non-vertebral fractures. There were higher risk for the vertebral fractures in two groups and higher risk for non-vertebral fractures in one group.

Conclusions

The results of the current study indicate that severe AC is associated with a significantly increased risk of vertebral fractures and non-vertebral fractures in postmenopausal women in China.     

Post Diagnosis Diet Quality and Colorectal Cancer Survival in Women

Background

Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival.

Methods

1201 women diagnosed with stage I–III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman.

Results

During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles = 0.71, 95% CI 0.52–0.98, p trend = 0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1 = 0.72, 95% CI = 0.43–1.21, p trend = 0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5–15 g/d = 1.30, 95%CI = 1.05–1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving = 1.11, 95% CI = 1.01–1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality.

Conclusion

Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations.     

Women Commencing Anastrozole,Letrozole or Tamoxifen for Early Breast Cancer: The Impact of Comorbidity and Demographics on Initial Choice

Background

Australian clinical guidelines recommend endocrine therapy for all women with hormone-dependent early breast cancer. Guidelines specify tamoxifen as first-line therapy for pre-menopausal women, and tamoxifen or an aromatase inhibitor (AI) for post-menopausal women depending on the risk of recurrence based on tumour characteristics including size. Therapies have different side effect profiles; therefore comorbidity may also influence choice. We examined comorbidity, and the clinical and demographic characteristics of women commencing different therapies.

Patients and Methods

We identified the first dispensing of tamoxifen, anastrozole or letrozole for women diagnosed with invasive breast cancer in the 45 and Up Study from 2004–2009 (N = 1266). Unit-level pharmacy and medical service claims, hospital, Cancer Registry, and self-reported data were linked to determine menopause status at diagnosis, tumour size, age, comorbidities, and change in subsidy restrictions. Chi-square tests and generalised regression models were used to compare the characteristics of women commencing different therapies.

Results

Most pre-menopausal women commenced therapy with tamoxifen (91%). Anastrozole was the predominant therapy for post-menopausal women (57%), followed by tamoxifen (28%). Women with osteoporosis were less likely to commence anastrozole compared with tamoxifen (anastrozole RR = 0.7, 95% CI = 0.5–0.9). Women with arthritis were 1.6-times more likely to commence letrozole than anastrozole (95% CI = 1.1–2.1). Tamoxifen was more often initiated in women with tumours >1 cm, who were also ≥75 years. Subsidy restriction changes were associated with substantial increases in the proportion of women commencing AIs (anastrozole RR = 4.3, letrozole RR = 8.3).

Conclusions

The findings indicate interplay of comorbidity and therapy choice for women with invasive breast cancer. Most post-menopausal women commenced therapy with anastrozole; however, letrozole and tamoxifen were more often initiated for women with comorbid arthritis and osteoporosis, respectively. Tamoxifen was also more common for women with tumours >1 cm and aged ≥75 years. Subsidy restrictions appear to have strongly influenced therapy choice.     

Curcumins-Rich Curry Diet and Pulmonary Function in Asian Older Adults

Background

Research on the effects of dietary nutrients on respiratory health in human populations have not investigated curcumin, a potent anti-oxidant and anti-inflammatory compound present principally in turmeric used in large amounts in Asian curry meals.

Objectives

To examine the association of curry intake with pulmonary function among smokers and non-smokers.

Design

The frequency of curry intake, respiratory risk factors and spirometry were measured in a population-based study of 2,478 Chinese older adults aged 55 and above in the Singapore Longitudinal Ageing Studies.

Results

Curry intake (at least once monthly) was significantly associated with better FEV₁ (b = 0.045±0.018, p = 0.011) and FEV₁/FVC (b = 1.14±0.52, p = 0.029) in multivariate analyses that controlled simultaneously for gender, age, height, height-squared, smoking, occupational exposure and asthma/COPD history and other dietary or supplementary intakes. Increasing levels of curry intake (‘never or rarely’, ‘occasional’, ‘often’, ‘very often’) were associated with higher mean adjusted FEV₁ (p for linear trend = 0.001) and FEV₁/FVC% (p for linear trend = 0.048). Significant effect modifications were observed for FEV₁ (curry* smoking interaction, p = 0.028) and FEV₁/FVC% (curry*smoking interaction, p = 0.05). There were significantly larger differences in FEV₁ and FEV₁/FVC% between curry intake and non-curry intake especially among current and past smokers. The mean adjusted FEV₁ associated with curry intake was 9.2% higher among current smokers, 10.3% higher among past smokers, and 1.5% higher among non-smokers.

Conclusion

The possible role of curcumins in protecting the pulmonary function of smokers should be investigated in further clinical studies.     

Increased Expression of Intranuclear Matrix Metalloproteinase 9 in Atrophic Renal Tubules Is Associated with Renal Fibrosis

Background

Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear.

Methods

This is a retrospective study. Institutional Review Board approval was obtained for the review of patients’ medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores.

Results

Patients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = −0.465, p<0.001) was an independent predictor of GFS.

Conclusions

Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.     

Alcohol Consumption and Viral Load Are Synergistically Associated with CIN1

Purpose

We investigated the association between alcohol consumption and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer, and determined whether these associations were modified by human papillomavirus (HPV) viral load in high-risk HPV-positive women participating in the Korean HPV cohort study (KHPV).

Methods

Among the women recruited in the KHPV (n = 1,243) from March 2006 to December 2009, we analyzed normal cytology (n = 581) as control group, CIN1 (n = 299), CIN2/3 (n = 161), or cervical cancer (n = 202). Multinomial logistic analysis was performed to estimate multivariate-adjusted odds ratios (OR).

Results

Alcohol drinkers had an increased risk of CIN1 (OR = 2.18, 95% CI 1.22–3.89) compared with non-drinkers after adjusting for potential confounders. Subjects with more frequent alcohol consumption had a higher risk of CIN1 (p for linear trend <0.0001). Higher ethanol consumption was associated with an increased risk of CIN1 (p for linear trend = 0.0001). We also observed a synergistic effect between HPV viral load and alcohol consumption: drinkers with a high HPV viral load (≥100 RLU/PC) were associated with a significantly increased risk of CIN1 (OR = 19.1; 95% CI, 6.60–55.3, interaction p<0.001). There were no associations between alcohol drinking and CIN2/3 or cervical cancer.

Conclusions

HPV viral load and alcohol was associated with the risk of CIN1 among high-risk HPV-positive women. This is the first demonstration that alcohol is an independent and combined risk factor of CIN1.     

Tree Nuts Are Inversely Associated with Metabolic Syndrome and Obesity: The Adventist Health Study-2

Objective

To examine the relationships of nut consumption, metabolic syndrome (MetS), and obesity in the Adventist Health Study-2, a relatively healthy population with a wide range of nut intake.

Research Design and Methods

Cross-sectional analysis was conducted on clinical, dietary, anthropometric, and demographic data of 803 adults. MetS was defined according to the American Heart Association and the National Heart, Lung, and Blood Institute diagnostic criteria. We assessed intake of total nuts, tree nuts and peanuts, and also classified subjects into low tree nut/low peanut (LT/LP), low tree/high peanut (LT/HP), high tree nut/high peanut (HT/HP), and high tree/low peanut (HT/LP) consumers. Odds ratios were estimated using multivariable logistic regression.

Results

32% of subjects had MetS. Compared to LT/LP consumers, obesity was lower in LT/HP (OR = 0.89; 95% CI = 0.53, 1.48), HT/HP (OR = 0.63; 95% CI = 0.40, 0.99) and HT/LP (OR = 0.54; 95% CI = 0.34, 0.88) consumers, p for trend = 0.006. For MetS, odds ratios (95% CI) were 0.77 (0.47, 1.28), 0.65 (0.42, 1.00) and 0.68 (0.43, 1.07), respectively (p for trend = 0.056). Frequency of nut intake (once/week) had significant inverse associations with MetS (3% less for tree nuts and 2% less for total nuts) and obesity (7% less for tree nuts and 3% less for total nuts).

Conclusions

Tree nuts appear to have strong inverse association with obesity, and favorable though weaker association with MetS independent of demographic, lifestyle and dietary factors.     

Association between Secreted Phosphoprotein-1 (SPP1) Polymorphisms and Low Bone Mineral Density in Women

Background

A recent meta-analysis found that secreted phosphoprotein-1 (SPP1) can predict the risk of both osteoporosis and fracture. No study has explored the association of SPP1 haplotype-tagging single nucleotide polymorphisms (htSNPs) and haplotypes with bone mineral density (BMD).

Methods

This is a cross-sectional study. A total of 1,313 healthy Taiwanese women aged 40 to 55 years were recruited from MJ Health Management Institute from 2009 to 2010. BMD was dichotomized into high and low BMD groups. Three common (allele frequency ≥5%) htSNPs were selected to examine the association between sequence variants of SPP1 and BMD.

Results

Homozygosity for the T allele of rs4754 were protective from low BMD [TT vs. CC: adjusted OR (AOR)  = 0.58, 95% confidence interval (CI)  = 0.83–0.89]. A protective effect was also found for women carrying 2 copies of Hap3 TCT (AOR  = 0.57, 95% CI  = 0.34–0.95). Menopausal status marginally interacted with SPP1 rs6839524 on BMD (p = 0.049). Postmenopausal women carrying variant rs6839524 (GG+GC vs. CC: AOR  = 2.35, 95% CI  = 1.06–5.20) or Hap1 TGC (AOR  = 2.36, 95% CI  = 1.06–5.24) were associated with 2.4-fold risk of low BMD. For women with low BMI (<18.5 kg/m²), variant rs6839524 (AOR  = 7.64) and Hap1 (AOR  = 6.42) were associated with increased risk of low BMD. These findings did not reach statistical significance after correction for multiple tests.

Conclusions

SPP1 htSNP protected against low BMD in middle-aged women. SPP1 genetic markers may be important for the prediction of osteoporosis at an early age.     

Association between Vitamin D Insufficiency and Elevated Serum Uric Acid among Middle-Aged and Elderly Chinese Han Women

Background

Association between vitamin D insufficiency and hyperuricemia has not been reported so far. We aimed to study the association of vitamin D insufficiency with elevated serum uric acid among middle-aged and elderly Chinese Han women.

Methods

We collected data from participants residing in Jinchang district of Suzhou from January to May, 2010. Serum uric acid, 25-hydroxy vitamin D and other traditional biomarkers including fasting plasma glucose and blood lipids were determined in 1726 women aged above 30 years. Association between vitamin D insufficiency and elevated uric acid was analyzed in premenopausal and postmenopausal women, respectively.

Results

Among postmenopausal women, 25-hydroxy vitamin D level of participants with elevated uric acid was lower than that of those with normal uric acid (median [interquartile range]: 35[28–57] vs 40[32–58], µg/L; P = 0.006). Elevated uric acid was more prevalent in participants with vitamin D insufficiency compared to those without vitamin D insufficiency (16.50% vs 8.08%; P<0.001). Association between vitamin D insufficiency and elevated uric acid was not significant among premenopausal women. However, participants with vitamin D insufficiency were more likely to have elevated uric acid compared with those without vitamin D insufficiency among postmenopausal women (OR, 95% CI: 2.38, 1.47–3.87). Moreover, after excluding individuals with diabetes and/or hypertension, the association of vitamin D insufficiency with elevated uric acid was still significant (OR, 95% CI: 2.48, 1.17–5.44).

Conclusions

Vitamin D insufficiency was significantly associated with elevated uric acid among postmenopausal Chinese Han women. This study suggested that a clinical trial should be conducted to confirm the association of vitamin D insufficiency with hyperuricemia.