ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms in relation to serum adiponectin levels and BMI in black and white women

Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single-nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study (SCCS) from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and BMI using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, P = 0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI.     

Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese

Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.     

Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City.

Apolipoprotein-E epsilon 4 (APOE-epsilon 4) has been consistently associated with Alzheimer disease (AD) and may be responsible for an earlier age at onset. We have previously reported a diminished association between APOE-epsilon 4 and AD in African Americans. Using a new method, which allows inclusion of censored information, we compared relative risks by APOE genotypes in an expanded collection of cases and controls from three ethnic groups in a New York community. The relative risk for AD associated with APOE-epsilon 4 homozygosity was increased in all ethnic groups (African American relative risk [RR]=3.0; 95% confidence interval [CI]=1.5-5.9; Caucasian RR=7.3, 95% CI=2.5-21.6; and Hispanic RR=2.5, 95% CI=1.1-5.7), compared with those with APOE-epsilon 3/epsilon 3 genotypes. The risk was also increased for APOE-epsilon 4 heterozygous Caucasians (RR=2.9, 95% CI=1.7-5.1) and Hispanics (RR=1.6, 95% CI=1.1-2.3), but not for African Americans (RR=0.6, 95% Ci=0.4-0.9). The age distribution of the proportion of Caucasians and Hispanics without AD was consistently lower for APOE-epsilon 4 homozygous and APOE-epsilon 4 heterozygous individuals than for those with other APOE genotypes. In African Americans this relationship was observed only in APOE-epsilon 4 homozygotes. These results confirm that APOE genotypes influence the RR of AD in Caucasians and Hispanics. Differences in risk among APOE-epsilon 4 heterozygote African Americans suggest that other genetic or environmental factors may modify the effect of APOE-epsilon 4 in some populations.     

Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.     

Association of FTO Gene Variants With Adiposity in African‐American Adolescents

The prevalence of obesity continues to increase significantly, with the largest rise in the African‐American adolescents. Genetic contributions to obesity are being identified with the advent of genome‐wide association studies (GWAS). Specifically, variants of the fat mass and obesity associated (FTO) gene have been associated with obesity in populations of European descent. The studies in African Americans have been inconclusive. To further evaluate the association of the FTO gene and adiposity in African Americans, we genotyped 47 single‐nucleotide polymorphisms (SNPs), including seven SNPs previously reported to be significant in the literature in a cohort consisting of 561 non‐Hispanic white and 497 African‐American individuals. Analysis of our data showed 17 SNPs to be associated with BMI Z‐score (BMI‐Z) in our study population. The strongest association was found in the African Americans. The most significant SNP was rs8057044, which was associated with BMI‐Z in the African Americans (P = 0.00054). SNP rs9939609 was found to be significant in the non‐Hispanic white population (P = 0.028). Our data confirm the association between FTO and adiposity suggesting that FTO is a childhood obesity susceptibility gene. Our data also identify a novel SNP of the FTO gene (rs8057044) that is associated with measures of adiposity in the African‐American population.     

The association of SNPs in ADIPOQ,ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents

Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag SNPs in these genes with insulin sensitivity was examined in a cohort of adolescents and their parents. Probands and siblings (n = 441, mean age = 17.9 years) were recruited along with their parents (n = 262, mean age = 47.9 years). Typed SNPs included 21 SNPs in ADIPOQ, 7 SNPs in ADIPOR1, and 13 SNPs in ADIPOR2. Mixed model linear regression was used to test the association of SNPs with euglycemic-clamp derived insulin sensitivity. All analyses were stratified by race. After corrections to account for multiple testing and the linkage disequilibrium structure of the genes, one SNP in the ADIPOQ gene (rs822393) was significantly associated with insulin sensitivity in white subjects. In whites, six SNPs in ADIPOQ, one SNP in ADIPOR1 and one SNP in ADIPOR2 were associated with insulin sensitivity at the P < 0.05 level. In African Americans, two SNPs in ADIPOR1 were associated with insulin sensitivity at the P < 0.05 level. These results suggest that a variant in the ADIPOQ gene influences levels of insulin sensitivity and age may modify the effects of this variant. There are several other variants in ADIPOQ, ADIPOR1, and ADIPOR2 that may influence insulin sensitivity and these variants should be further investigated in other populations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Self-reported comorbidities among self-described overweight African-American and Hispanic adults in the United States: results of a national survey

Objective: To examine the concordance between self‐described weight status and BMI, the prevalence of self‐reported comorbidities, and the association between comorbidities and self‐rated health among overweight African‐American and Hispanic US adults. Methods and Procedures: A nationally representative sample of 537 African‐American and 526 Hispanic adults who were identified using a combination of random digit dialing and listed household sampling and self‐described as being slightly or very overweight participated in a telephone interview. Self‐reported height and weight were used to calculate BMI. Results: More than half of African Americans (56%) and one‐third of Hispanics (34%) who self‐described as “slightly” overweight would be classified as obese based on BMI. One‐third (33%) of African Americans reported high blood pressure, followed by arthritis (20%), high cholesterol (18%), and diabetes (15%). Among Hispanics, high cholesterol was the most frequently reported comorbidity (17%), followed by high blood pressure (15%), and difficulty sleeping (12%). Almost three‐quarters of African Americans surveyed (72%) reported that their overall health was good to excellent compared to 62% for Hispanics. Discussion: Self‐reported rates of obesity‐related comorbidities fall below what would be expected based on prevalence data derived from physiologic measures, suggesting a lack of awareness of actual risk. Despite the greater self‐reported prevalence of certain risk factors for poor health, African Americans have a more optimistic view of their overall health and weight status compared to Hispanics. Physicians have an important opportunity to communicate to their minority patients the serious health consequences associated with excess weight.     

Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population

Adiponectin is inversely associated with the risk of ischemic stroke through its anti-inflammatory and anti-atherogenic effects. Genetic variations in the adiponectin gene (ADIPOQ) have been shown to be associated with the risk of ischemic stroke in Caucasians and Japanese populations. However, it was unknown whether variations in the ADIPOQ gene were associated with the risk of ischemic stroke in Chinese population. A case-control study was performed among 302 patients with ischemic stroke and 338 unrelated controls in a Chinese Han population. The single-nucleotide polymorphisms (SNPs) rs266729 (−11377C/G), rs2241766 (+45T/G), rs1501299 (+276G/T) in the ADIPOQ gene were genotyped by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GG genotype and G allele of rs266729 in the patients with ischemic stroke were significantly higher than those in the controls (P = 0.034, P = 0.010, respectively). In univariate logistic analysis, compared with CC genotype, GG genotype of rs266729 increased the risk of ischemic stroke (odds ratio (OR) = 2.062, 95% confidence interval (CI) = 1.145–3.715, P = 0.016). After adjustment for potential risk factors by the multivariate logistic analysis, rs266729 remained positive correlation with ischemic stroke (OR = 2.165; 95% CI = 1.116–4.197, P = 0.022). However, no significant association was observed among rs2241766, rs1501299 and ischemic stroke. In addition, no significant difference was found in haplotype frequencies between the patients with ischemic stroke and control subjects. The present study demonstrated that the promoter polymorphism rs266729 of the ADIPOQ gene was associated with an increased risk of ischemic stroke in the Chinese Han population.     

Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study

Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (P values of 0.011 and 0.034), and associated or trending towards association with SAT (P values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.     

Interethnic differences in muscle, liver and abdominal fat partitioning in obese adolescents

The prevalence of insulin resistance and type 2 diabetes (T2D) in obese youth is rapidly increasing, especially in Hispanics and African Americans compared to Caucasians. Insulin resistance is known to be associated with increases in intramyocellular (IMCL) and hepatic fat content. We determined if there are ethnic differences in IMCL and hepatic fat content in a multiethnic cohort of 55 obese adolescents. We used (1)H magnetic resonance spectroscopy (MRS) to quantify IMCL levels in the soleus muscle, oral glucose tolerance testing to estimate insulin sensitivity, magnetic resonance imaging (MRI) to measure abdominal fat distribution. Liver fat content was measured by fast-MRI. Despite similar age and % total body fat among the groups, IMCL was significantly higher in the Hispanics (1.71% [1.43%, 2.0%]) than in the African-Americans (1.04% [0.75%, 1.34%], p = 0.013) and the Caucasians (1.2% [0.94%, 1.5%], p = 0.04). Liver fat content was undetectable in the African Americans whereas it was two fold higher than normal in both Caucasians and Hispanics. Visceral fat was significantly lower in African Americans (41.5 cm(2) [34.6, 49.6]) and was similar in Caucasians (65.2 cm(2) [55.9, 76.0]) and Hispanics (70.5 cm(2) [59.9, 83.1]). In a multiple regression analysis, we found that ethnicity independent of age, gender and % body fat accounts for 10% of the difference in IMCL. Our study indicates that obese Hispanic adolescents have a greater IMCL lipid content than both Caucasians and African Americans, of comparable weight, age and gender. Excessive accumulation of fat in the liver was found in both Caucasian and Hispanic groups as opposed to virtually undetectable levels in the African Americans. Thus, irrespective of obesity, there seem to be some clear ethnic differences in the amount of lipid accumulated in skeletal muscle, liver and abdominal cavity.     

Mammography screening and breast self-examination among minority women in public housing projects: the impact of physician recommendation.

This exploratory study examined the impact of physician recommendations and other factors on mammography screening and breast-self examination (BSE) among African American and Hispanic women in public housing communities. We surveyed a randomly selected sample of low-income households from three low-income communities (n = 291), which included both African Americans and Hispanic women. Data for this paper are reported only on women who were 40 years and older head of the households (n = 120 women, including 74 Hispanics and 46 African Americans), since they meet the age criterion for mammography screening. Our analyses indicated that only 46% of women obtained mammography in the previous 12 months, with no significant differences between the Hispanic and African American women in mammography rates. Physicians' recommendations were among the most significant and substantial predictors of obtaining a mammogram or performing BSE. Further, odds were also higher for those who had insurance coverage. In addition, our data also indicated that almost one out of four women, aged 40 and older participants in this study, claimed that their health care providers never told them they needed a mammogram or never told them that they should perform BSE, with no significant differences between Hispanic and African Americans. Our analyses points to an urgent need for intervention to inform and motivate the service providers in underserved communities to motivate breast cancer screening (BCS) among minority women. Additionally, our examination points to the need for urgent interventions targeting minority women, particularly women with no medical insurance for breast cancer screening.     

Variants in the Adiponectin Gene and Serum Adiponectin: The Coronary Artery Development in Young Adults (CARDIA) Study

Circulating adiponectin is involved in the atherosclerotic process and has been associated with cardiovascular disease as well as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The adiponectin gene (ADIPOQ) encodes the circulating protein adiponectin and affects its expression. Only a small proportion of all known ADIPOQ polymorphisms have been investigated in relation to circulating adiponectin concentrations. Using data from 3,355 African‐American and white men and women aged 33–45 at the year 15 examination from the Coronary Artery Development in Young Adults (CARDIA) Study the association between 10 single‐nucleotide polymorphisms (SNPs) within ADIPOQ and serum adiponectin was examined using linear regression. SNPs were chosen based on a tagSNP approach. Models were stratified by self‐reported race to control for population stratification, and Bonferroni corrected for multiple comparisons. ADIPOQ SNPs rs17300539 (P < 0.0001), rs182052 (P = 0.0013), rs822393 (P = 0.0005), rs9882205 (P = 0.0001), and rs3774261 (P = 0.0001) were strongly associated with serum adiponectin concentrations in whites. In general, there was a dose‐response relationship of adjusted mean adiponectin concentrations across genotypes. Only one SNP, rs17300539 was marginally associated with serum adiponectin concentrations (P = 0.0087) in African Americans. Significant interactions were found between waist and rs182052 (P = 0.0029) and between rs9882505 and smoking (P = 0.001) in whites. Many ADIPOQ SNPs have not yet been examined, and additional studies are needed to determine whether these may be functional variants.     

Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations

The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 μg/L (cases) and controls (SF >100 μg/L in men, SF >50 μg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7 × 10(-6)) and replicated in African Americans (p = 0.0012).Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4 × 10(-5)); six SNPs replicated in other ethnicities (p<0.01). SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0 × 10(-5)). These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.     

Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.     

Racial disparities in clinical presentation,surgical procedures,and hospital outcomes among patients with hepatocellular carcinoma in the United States

BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States (US), with substantial disparities observed in cancer incidence and survival among racial groups. This study provides analyses on race and ethnicity disparities for patients with HCC.MethodsThis is a cross-sectional analysis of data from the National Inpatient Sample (NIS) between 2011 and 2016, utilizing the STROBE guidelines. Multivariate logistic regression analyses were used to examine the risk-adjusted associations between race and pre-treatment clinical presentation, surgical procedure allocation, and post-treatment hospital outcomes. All clinical parameters were identified using ICD-9-CM and ICD-10-CM diagnosis and procedure codes.Results83,876 weighted HCC hospitalizations were reported during the study period. Patient demographics were divided according to NIS racial/ethnic categorization, which includes Caucasian (57.3%), African American (16.9%), Hispanic (15.7%), Asian or Pacific Islanders (9.3%), and Native American (0.8%). Association between greater odds of hospitalization and Elixhauser Comorbidity Index > 4 was significantly higher among Native Americans (aOR=1.79; 95% CI: 1.23–2.73), African Americans (aOR=1.24; 95% CI: 1.12–1.38), and Hispanics (aOR=1.11; 95% CI, 1.01–1.24). Risk-adjusted association between race and receipt of surgical procedures demonstrated that the odds of having surgery was significantly lower for African Americans (aOR=0.64; 95% CI: 0.55–0.73) and Hispanics (aOR=0.70; 95% CI: 0.59–0.82), while significantly higher for Asians/Pacific Islanders (aOR=1.36; 95% CI: 1.28–1.63). Post-operative complications were significantly lower for African Americans (aOR=0.68; 95% CI: 0.55–0.86) while the odds of in-hospital mortality were significantly higher for African Americans (aOR=1.28; 95% CI: 1.11–1.49) and Asians/Pacific Islanders (aOR=1.26; 95% CI: 1.13–1.62).ConclusionsAfter controlling for potential confounders, there were significant racial disparities in pre-treatment presentations, surgical procedure allocations, and post-treatment outcomes among patients with HCC. Further studies are needed to determine the underlying factors for these disparities to develop targeted interventions to reduce these disparities of care.     

The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer

To study the role of the adiponectin (ADIPOQ) gene single-nucleotide polymorphism (SNP) in the susceptibility and prognosis for non-small cell lung cancer (NSCLC), we recruited 344 patients with NSCLC, of which 141 had undergone surgical resection and post-surgery follow up.?For controls, there were 264 healthy volunteers for the control group, matched in age and sex with the NSCLC patients. Genotyping of SNPs in the ADIPOQ gene, namely, rs266729 (11365C>G); rs822395 (4034A>C); rs822396 (3964A>G); rs2241766 (+45T>G) were performed. Of all SNPs in the ADIPOQ gene, only the TT genotype and T allele frequency of the rs2241766 were more prevalent in NSCLC subjects than in controls. The TT genotype of rs2241766 was significantly associated with susceptibility to NSCLC before and after adjustment for age, sex, body mass index, and smoking status. In the survival analyses of subjects receiving surgical resection, only the SNPs of rs2241766 were significantly related to overall survival of NSCLC. Our results suggest that the SNP rs2241766 of the ADIPOQ gene may determine both susceptibility to NSCLC, and the prognosis for those who underwent surgical treatment.     

Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study

For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (~20,000), African American (~9,000), American Indian (~6,000), Mexican American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific Islander/Native Hawaiian (~175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits.     

Associations of Genetic Variants in the PSCA,MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.     

Ten-Year Trends in Coronary Calcification in Individuals without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

Background

Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known.

Methods and Findings

To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55–84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000–02, 50.4% in 2003–04, 60.0% is 2005–06, 57.4% in 2007–08, and 61.3% in 2010–12 (p for trend <0.001). The trend was strongest among African Americans aged 55–64 [prevalence ratio for 2010–12 vs. 2000–02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence.

Conclusions

There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.