Predictive impact of coronary risk factors in southern Croatia: a case control study

The aim of study was to compare the impact of coronary risk factors on the incidence of acute myocardial infarction (MI) between Croatia, Central and Eastern Europe, and the rest of the world. As a part of the large international INTERHEART case-control study of acute MI in 52 countries (15,152 cases and 14,820 controls) we have investigated the relationship between several known risk factors (smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins, and psychosocial factors) and MI among patients without previously known coronary heart disease in Southern Croatia. The main identified MI risk factors in Southern Croatia were heavy smoking (>20 cig/day; OR 3.86; 95% CI 2.31-6.46), diabetes mellitus (OR 2.83; 95% CI 1.58-5.23), abnormal ratio of B-100 and A-1 apolipoproteins (OR 2.23; 95% CI 1.28-3.89), elevated waist to hip ratio (OR 1.96; 95% CI 1.21-3.18), and arterial hypertension (OR 1.68; 95% CI 1.15-2.45). Protective was moderate alcohol consumption (OR 0.63; 95% CI 0.40-0.99). The prevalence of major MI risk factors in Croatia is similar to that in the surrounding countries and in the world, accounting for over 90% of the population attributable risk. However, physical activity, dietary and psychosocial factors are seemingly less important in this country, while moderate alcohol consumption is more protective than regionally or globally.     

Cardiometabolic Risk Profiles Associated with Chronic Complications in Overweight and Obese Type 2 Diabetes Patients in South China

Background

Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated.

Methods

We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m² who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted.

Results

Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88).

Conclusions

Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.     

Hypertriglyceridemic waist may explain ethnic differences in hypertension among patients with type 2 diabetes in Sweden

ABSTRACT: BACKGROUND: Hypertension is common among persons with type 2 diabetes. The aim of this study was to analyze the association between ethnicity and hypertension prevalence after adjusting for age, sex, Hba1c, total cholesterol, elevated triglycerides and hypertriglyceridemic waist. The study population consisted of 354 primary health care patients diagnosed with type 2 diabetes (173 Assyrians/Syrians and 181 Swedes) residing in Sodertalje, Sweden. Unconditional logistic regression was used to analyze the data. RESULTS: Hypertension prevalence was higher among Swedes than Assyrians/Syrians, (77% versus 58%; p = 0.001). In the unadjusted logistic regression model, the odds ratio for hypertension in Swedes was twice as high than that in Assyrians/Syrians (OR = 2.44; 95% CI =1.54 - 3.86). In the age- and sex-adjusted model, odds ratio of hypertension was 2.25 (95% CI 1.41-3.60). After adjustments for total cholesterol was made, the odds ratio of hypertension decreased slightly to 1.73. When elevated triglycerides and hypertriglyceridemic waist were separately introduced, the odds ratio of hypertension was no longer significant between the ethnic groups (1.60 and 1.43 for triglycerides and hypertriglyceridemic waist respectively). In addition, advanced age - 60-69 years old (OR = 1.80, CI 95% 1.00-3.20) and [greater than or equal to] 70 years old (OR = 2.88, CI 95% 1.40-5.93), elevated total cholesterol (OR = 1.48, CI 95% 1.12-1.95) and presents of hypertriglyceridemic waist (those with high WC and high TG) were significant confounding factors for the increased risk of hypertension independent of ethnicity. CONCLUSIONS: The crude differences in prevalence of hypertension between the Swedes and Assyrians/Syrians in our study population with type 2 diabetes were no longer significant when adjusting for high triglycerides levels or the presence of hypertriglyceridemic waist.     

Trace element status in Saudi patients with established atherosclerosis

BACKGROUND: Traditional coronary risk factors do not fully explain variations in the incidence of cardiovascular disease (CVD). Epidemiological studies have implicated perturbations in selenium, copper, and zinc metabolism in the aetiology of CVD. However, these studies have been principally undertaken in Caucasian populations, in whom trace element intake is generally sufficient. METHOD: We have measured serum and urine selenium, copper, and zinc; and superoxide dismutase, glutathione peroxidase, and lipid peroxide concentrations in 130 Saudi male subjects with established CVD, and 130 age-matched controls. RESULTS: Diabetes mellitus, positive smoking habit (p<0.0001 for both), and hypertension (p<0.05) were more prevalent among CVD patients. Urinary copper (p<0.0001) and zinc (p<0.05) were higher among controls. Serum selenium concentrations were lower among CVD patients (p<0.001), and a high proportion (52%) had selenium levels below 79mug/L compared to controls (22%) (p<0.0001). Conditional logistic regression analysis, showed the characteristics differentiating CVD patients from controls were serum zinc (odds ratio (OR) 0.92, confidence interval (CI) 0.85-0.99, p<0.05), serum copper/zinc ratio (OR 0.31, CI 0.10-0.96), serum selenium (OR 0.07, CI 0.02-0.31, p<0.0001), and urine selenium (OR 3.34, CI 1.40-7.99, p<0.01). CONCLUSION: Measures of trace metals status appear to be associated with the risk of atherosclerosis in a Saudi male population.     

CYP17, SRD5A2, CYP1B1, and CYP2D6 gene polymorphisms with prostate cancer risk in North Indian population

To investigate the involvement of the CYP17, SRD5A2, CYP1B1, and CYP2D6 variants with prostate cancer, a case-control study of 100 patients and an equal number of age-matched control men was conducted. There appears to be a nonsignificant increase with risk of prostate cancer for individuals carrying one copy of the CYP17 A2 allele (OR, 1.80; 95% CI, 0.99-3.29, P=0.05). The risk was increased in individuals having two A2 alleles (OR; 2.81, 95% CI, 1.06-7.40, P=0.03). Compared with men having the VV genotype of SRD5A2 gene, there was no significant association between the VL genotype and the risk of prostate cancer (OR; 0.54, 95% CI; 0.29-1.03, P=0.06). There was no difference in the occurrence of the genotype LL between controls and prostate cancer patients (OR; 0.90, 95% CI; 0.43-1.89, P=0.79). There was a nonsignificant increased risk of prostate cancer for individuals carrying the CYP1B1Leu/Val genotype (OR, 1.70, 95% CI, 0.91-3.17, P =0.09), which was increased in those having the Val/Val allele (OR, 3.38; 95% CI, 1.13-10.07, P=0.02). Relative to men homozygous for the wild-type allele in CYP2D6 gene, those heterozygous for the B allele had an odds ratio of 1.78 (95% CI, 0.76-4.17, P=0.18) for patients, and for homozygous individuals, it was 1.95 (0.55-6.93, P=0.30). These observations have suggested that the CYP17 A2/A2, CYP1B1 Val/Val, and CYP2D6 genotypes may be associated with an altered risk of prostate cancer, while the CYP2D6 and SRD5A2 V89L polymorphism have no association with its risk in the North Indian population.     

Association of polymorphous markers Pro72Arg and C(-594)CC OF TP53 gene with diabetic polyneuropathy in patients with type 1 diabetes mellitus living in Moscow

The aim of this study was the search of association of polymorphous markers Pro72Arg and C(-594)CC of TP53 gene with diabetic polyneuropathy (DPN) in patients with type 1 diabetes mellitus with or without clinical signs of DPN. We have found that polymorphous marker Pro72Arg of TP53 gene was associated with DPN in Russian patients with type 1 diabetes mellitus living in Moscow. The carriers of Arg allele and Arg/Arg genotype had higher risk of DPN development (OR = 1.96; CI = 1.32-2.90; and OR = 2.14; CI = 1.23-3.73; relatively). On the contrary, the carriage of Pro allele was associated with the lower risk of DPN development (OR = 0.51; CI = 0.34-0.76). We have not found any association of polymorphous marker C(-594)CC of TP53 gene with DPN in Russian patients with type 1 diabetes mellitus living in Moscow.     

Interactions between <Emphasis Type="Italic">CYP1A1</Emphasis> polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies

The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99–1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile–Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta-analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC.     

Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese

The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population.     

Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis

Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD]?=?1.203, 95 % CI 0.795–1.611, P?<?0.001). There were also obviously increased levels of serum TNF-α in diabetic patients with DPN when compared with healthy controls (SMD?=?2.364, 95 % CI 1.333–3.394, P?<?0.001). In addition, there were increased serum TNF-α levels in painful DPN patients compared with painless DPN patients (SMD?=?0.964, 95 % CI 0.237–1.690, P?=?0.009). High level of serum TNF-α was significantly associated with increased risk of DPN in patients with type 2 diabetes (odds ratio [OR]?=?2.594, 95 % CI 1.182–5.500, P?=?0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR?=?2.486, 95 % CI 0.672–9.193, P?=?0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.     

The Relationship between Nonalcoholic Fatty Liver Disease and Retinopathy in NHANES III

BackgroundNonalcoholic fatty liver disease (NAFLD), an emerging multisystem disease, has the similar pathogenesis with diabetes and is prevalent in diabetes. This study investigated whether NAFLD is associated with retinopathy in individuals with diabetes and without diabetes.MethodsThe association between NAFLD and retinopathy was investigated in 5963 participants aged 40 years and older who participated in the NHANES III, a nationally representative, population-based and cross-sectional study. NAFLD was detected via ultrasonography, and fundus photographs were obtained to grade retinopathy patterns. We performed multivariate logistic regression analysis to investigate the relationship between the presence of retinopathy and NAFLD and diabetes.ResultsAfter adjusting for multiple covariates, NAFLD population had no evidence of retinopathy increase in population without diabetes (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.48 to 1.26). In addition, NAFLD in individuals with diabetes was not significantly associated with retinopathy (OR: 0.77; 95% CI: 0.47 to 1.26), independent of age, gender, ethnicity, waist circumference, serum high-density lipoprotein (HDL) cholesterol, serum triglycerides, systolic blood pressure, and glycated hemoglobin.ConclusionsIn the US general population, NAFLD is not a precipitating factor of retinopathy in population with or without diabetes.     

Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes

High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p<0.0001 for all). In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI), waist circumference, diabetes duration, glycated hemoglobin (HbA1c), albumin creatinine ratio (ACR) and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE)= -2.19 (0.59), p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE)=-4.42(1.16) ml/min/1.73m² vs. -1.50 (0.67) ml/min/1.73m², respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m² increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21–1.64) in SGR sample, 53% (OR = 1.53; 95% CI 1.21–1.94) in FG sample, and 44% (OR = 1.44; 95%CI 1.27–1.64) in the two studies considered together (p<0.0001 for all). In the combined sample, further adjustment for the above mentioned covariates did not change the observed association (OR = 1.36; 95%CI 1.16–1.60; p<0.0001). Our study, so far the largest addressing the relationship between serum adiponectin and GFR in T2D, strongly suggests that the paradoxical inverse association, previously reported in different clinical sets, is also observed in diabetic patients. Further studies are needed to unravel the biology underlying this counterintuitive relationship.     

Alcohol consumption patterns of shiftworkers compared with dayworkers

The detrimental effects of excessive alcohol consumption are well documented. There is some evidence that shiftworkers consume more alcohol than dayworkers as a sleep aid to compensate for sleep difficulties associated with work schedules. This study investigated drinking patterns between shiftworkers and dayworkers using the 2006 and 2007 waves from the Household Income and Labour Dynamics Survey. A subset of workers who were not in full-time study and had a single job were selected; participants who did not drink alcohol (n = 2090) were excluded. Using the 2001 Australian Government alcohol guidelines, alcohol consumption for risk of short-term harm (7+ standard drinks for men, 5+ for women) was investigated. The number of workers who drank alcohol "nearly every day" or "every day" was also examined. Some 13% of shiftworkers and 10% of those on standard schedules reported consuming alcohol at levels risky for short-term harm. Having a child less than 17 yrs (odds ratio [OR]?=?.39, 95% confidence interval [CI]?=?.22-.69), higher job demands (OR =?.71, 95% CI =?.58-.86), being female (OR =?.45, 95% CI=. 26-.79), and being older (OR =?.89, 95% CI =?.87-.92) significantly reduced, whereas being a shiftworker (OR = 2.10, 95% CI = 1.08-4.12) significantly increased, the odds of drinking alcohol in short-term risky levels. Nearly 10% of shiftworkers and 8% of those on standard schedules reported consuming alcohol in short-term risky levels at least weekly. Having a child less than 17 yrs (OR =?.40, 95% CI =?.22-.74), higher job demands (OR =?.69, 95% CI =?.56-.86), being female (OR =?.28, 95% CI =?.15-.53), and being older (OR =?.92, 95% CI =?.89-.94) were associated with a significant reduction in the odds of consuming alcohol at risky levels at least weekly. Being a shiftworker was not associated with a significant increase in the odds of consuming alcohol at such risky levels at least weekly, but a trend was evident (OR = 1.47, 95% CI =?.73-3.00). Some 13.5% of shiftworkers and 21% of those on standard schedules reported consuming alcohol in any amount "near daily" or "daily." Working more hours than preferred (OR = 1.80, 95% CI = 1.12-2.89) and being older (OR = 1.10, 95% CI = 1.07-1.13) were associated with a significant increase, and being female (OR =?.18, 95% CI =?.10-.33), and being a shiftworker (OR =?.20, 95% CI =?.09-.45) were associated with a significant decrease in the odds of consuming alcohol "daily" or "near daily." Overall, the results suggest that shiftworkers may be more likely to consume alcohol at levels considered to be risky for health in the short term. In contrast, they appear less likely to drink alcohol daily. This pattern is suggestive of "binge drinking" behavior.     

Total Body Adiposity,Triglycerides, and Leg Fat are Independent Risk Factors for Diabetic Peripheral Neuropathy in Chinese Patients with type 2 Diabetes Mellitus

Objective: To evaluate the risk factors associated with diabetic peripheral neuropathy (DPN) in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: Between January 2014 and December 2017, 107 participants who had obesity with T2DM and 349 participants who had normal weight with T2DM, matched for age, sex, and duration of diabetes, were recruited. The clinical and biochemical parameters were measured in each patient. DPN was diagnosed based on neuropathy symptom score and neuropathy deficit score. Motor and sensory nerve conduction velocities were measured by electromyography. Body fat mass was estimated by dual-energy X-ray absorptiometry, while hepatic steatosis was evaluated by ultrasonography.Results: The group with obesity had a significant higher prevalence of DPN (66.62%) than that (46.99%) of the group with normal weight. Compared to the patients with normal weight, the sural sensory nerve in the right lower limbs of the patients with obesity was more susceptible to damage. Hypertriglyceridemia in the patients with obesity was a significant independent risk factor for DPN (odds ratio &lsqb;OR], 3.90 &lsqb;95% confidence interval (CI), 1.01 to 15.02]; P = .04), while the duration of diabetes (OR, 1.33 &lsqb;95% CI, 1.07 to 1.65]; P<.01) and leg subcutaneous fat mass (OR, 0.72 &lsqb;95% CI, 0.57 to 0.90]; P<.01) in the patients with normal weight were independent risk factors for DPN. The presence of obesity alone in patients with T2DM could predict high DPN risk (OR, 3.09 &lsqb;95% CI, 1.11 to 8.65]; P = .04).Conclusion: Reducing total body adiposity and triglyceride levels, as well as avoiding leg subcutaneous fat atrophy, could be new prevention strategies for DPN in Chinese patients with T2DM.Abbreviations: ALB = albumin; ALT = alanine transaminase; AST = aspartate transaminase; AUC = area under the curve; AUCc-p/AUCglu = AUC of C-peptide/AUC of glucose; BMI = body mass index; BP = blood pressure; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; DPN = diabetic peripheral neuropathy; FC-P = fasting C-peptide; FPG = fasting plasma glucose; FFA = free fatty acid; γ-GGT = γ-glutamyl transferase; HbA1c = glycated hemoglobin A1c; HDL-C = high-density-lipoprotein cholesterol; ISI = insulin sensitivity index; ISSI-2 = insulin secretion-sensitivity index-2; LDL-C = low-density-lipoprotein cholesterol; MNCS = motor nerve conduction velocity; OGTT = oral glucose tolerance test; PG = plasma glucose; SAT = subcutaneous adipose tissue; SBP = systolic blood pressure; SNCS = sensory nerve conduction velocity; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; UA = uric acid; VAT = visceral adipose tissue; WC = waist circumference     

Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma

Introduction: Glioma is one of the most aggressive human tumors; however, little is known about its genetic risk factors. The role of heredity is likely to be explained by combinations of common low-risk variants. Previous studies have indicated that more than 100 single nucleotide polymorphisms (SNPs) are associated with the risk of glioma. Methods: To further investigate how and to what extent these SNPs contribute to glioma susceptibility in a Chinese population, we analyzed 43 SNPs of 226 glioma patients and 254 normal people in order to evaluate the associations between SNPs and the risk of glioma. Results: Overall, we found three protective alleles for glioma in patients: the allele "G" of rs1801275 in the IL4R gene by allele model (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.50-0.99; P=0.04) and dominant model (OR, 0.67; 95% CI, 0.46-0.99; P=0.04) analysis respectively, the allele "T" of rs17748 in the TREH gene by recessive model (OR, 0.48; 95% CI, 0.23-1.01; P=0.05) analysis, and the allele "G" of rs6470745 in CCDC26 gene by recessive model (OR, 0.48; 95% CI, 0.26-0.89; P=0.02) analysis. Conclusion: This study provides evidence for three glioma susceptibility genes - TREH, IL4R and CCDC26 - in a Chinese population; this may shed light on molecular markers of glioma susceptibility and could therefore be used as a diagnostic and prognostic marker for glioma patients in clinical study.     

Fibroblast growth factor receptor 4 polymorphisms and coronary artery disease: a case control study

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in vascular system. FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to coronary artery disease (CAD) in the Chinese population. We identified three polymorphisms in the FGFR4 gene, rs351855G/A (Gly388Arg), rs145302848C/G and rs147603016G/A, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 658 CAD cases and 692 healthy controls. Results showed that frequencies of GA genotype, AA genotype and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls [odds ratio (OR) = 0.79, 95 % confidence intervals (CI) 0.62-0.99, P = 0.042; OR = 0.58, 95 % CI 0.41-0.81, P = 0.002; and OR = 0.77, 95 % CI 0.66-0.90, P = 0.001, respectively]. The rs147603016GA genotype and A allele also showed lower numbers in CAD cases (OR = 0.58, 95 % CI 0.36-0.93, P = 0.025; and OR = 0.59, 95 % CI 0.40-0.95, P = 0.028). The rs145302848C/G polymorphism did not show any correlation with CAD. Haplotype analysis revealed that the prevalence of ACG haplotype (rs351855, rs145302848 and rs147603016) was significantly decreased in CAD patients (P = 0.002). Our data suggested that the FGFR4 rs351855G/A (Gly388Arg) and rs147603016G/A polymorphisms could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.     

Lactation and cardiovascular risk factors in mothers in a population-based study: the HUNT-study

ABSTRACT: BACKGROUND: Lactation has beneficial short term effects on maternal metabolic health, but the long term effects are less well known. METHODS: We studied the association between lifetime duration of lactation and cardiovascular risk factors in mothers later in life among 21,368 parous women aged 20 to 85 years attending the second Nord-Trondelag Health Study (HUNT2) in 1995-1997, Norway, a cross-sectional population-based study. General linear modelling was used to calculate mean values of known cardiovascular risk factor levels in five categories of lifetime duration of lactation. Logistic regression was conducted to estimate odds ratios of hypertension, obesity and diabetes. RESULTS: Among women aged 50 years or younger, lifetime duration of lactation was significantly and inversely associated with body mass index (P-trend, < 0.001), waist circumference (P-trend, < 0.001), systolic and diastolic blood pressure (both P-trends, < 0.001), and serum levels of triglycerides, total cholesterol and low density lipoprotein cholesterol (all P-trends, < 0.001) after adjustment for covariates. Parous women aged 50 years or younger who had never lactated had higher prevalence of hypertension, obesity and diabetes. In this age group, compared to women who had lactated for 24 months or more, parous women who had never lactated had an OR for hypertension of 1.88 (95% CI 1.41, 2.51), an OR for obesity of 3.37 (95% CI 2.51, 4.51) and an OR for diabetes of 5.87 (95% CI 2.25, 15.3). Among women older than 50 years there were no clear associations. CONCLUSION: Lifetime duration of lactation was associated with long term reduced cardiovascular risk levels in mothers aged 50 years or younger.     

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.     

The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach

Background

Adiposity, assessed as elevated body mass index (BMI), is associated with increased risk of ischemic heart disease (IHD); however, whether this is causal is unknown. We tested the hypothesis that positive observational associations between BMI and IHD are causal.

Methods and Findings

In 75,627 individuals taken from two population-based and one case-control study in Copenhagen, we measured BMI, ascertained 11,056 IHD events, and genotyped FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238). Using genotypes as a combined allele score in instrumental variable analyses, the causal odds ratio (OR) between BMI and IHD was estimated and compared with observational estimates. The allele score-BMI and the allele score-IHD associations used to estimate the causal OR were also calculated individually. In observational analyses the OR for IHD was 1.26 (95% CI 1.19–1.34) for every 4 kg/m² increase in BMI. A one-unit allele score increase associated with a 0.28 kg/m² (95 CI% 0.20–0.36) increase in BMI and an OR for IHD of 1.03 (95% CI 1.01–1.05) (corresponding to an average 1.68 kg/m² BMI increase and 18% increase in the odds of IHD for those carrying all six BMI increasing alleles). In instrumental variable analysis using the same allele score the causal IHD OR for a 4 kg/m² increase in BMI was 1.52 (95% CI 1.12–2.05).

Conclusions

For every 4 kg/m² increase in BMI, observational estimates suggested a 26% increase in odds for IHD while causal estimates suggested a 52% increase. These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia, and type 2 diabetes. This work has important policy implications for public health, given the continuous nature of the BMI-IHD association and the modifiable nature of BMI. This analysis demonstrates the value of observational studies and their ability to provide unbiased results through inclusion of genetic data avoiding confounding, reverse causation, and bias. Please see later in the article for the Editors'' Summary