Serum 25-hydroxyvitamin D,genetic susceptibility,and the risk of incident type 2 diabetes:A prospective cohort in East China

Background:The serum vitamin D level varies widely by population,and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus(T2DM).However,the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear.The study aimed to investigate the association between serum 25-hydroxyvitamin D(25[OH]D)levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition.Methods:In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors(SPECT-China)cohort,1862 participants free of T2DM at baseline were included.A weighted genetic risk score was calculated with 28 variants associated with T2DM.Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM.Results:After a 5-year follow-up,132 cases of T2DM were documented.We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment(χ^(2)=0.571,P_(for trend)=0.426).Compared to those in the lowest quartile of 25(OH)D,the odds ratios(ORs)(95%confidence interval[CI])for participants with increased quartiles were 1.29(0.74-2.25),1.35(0.77-2.36),and 1.27(0.72-2.24),respectively.We observed a positive association of glycated hemoglobin(HbA1c)with 25(OH)D at baseline(β=1.752,P=0.001)and after follow-up(β=1.385,P=0.003),and a negative association of ln conversion homeostasis model assessment(HOMA)-βwith 25(OH)D at baseline(β=-0.982,P=0.021).There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM(χ^(2)=2.710,P_(for interaction)=0.100).The lowest OR(95%CI)of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D(0.17[0.05-0.62]).Conclusion:Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

5-HTR2A Polymorphisms rs6311 and rs6313 and Major Depressive Disorder: A Meta-Analysis

rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I2. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.

Genetic variation of low-density lipoprotein-cholesterol and its clinical implications

Plasma lipids are controlled by genes and play an important role in the development of atherosclerosis. Dysplipidemia is an important risk factor for coronary artery disease (CAD). Coronary artery disease is the leading cause of mortality and morbidity in the developed world. More than 14 million Americans are afflicted with clinically significant CAD.~1 To illustrate the impact of CAD in developed countries, the medical and societal costs of CAD in the United States alone are in excess of $90 billion annually.~1 More than (600 000) Americans each year develop new cardiac events, more than 10% of which occur in Americans (<50) years of age.~1 Identifying genetic predisposition to early onset of CAD could help in understanding basic disease mechanism, guiding targeted preventive efforts, and planning appropriate therapeutic strategies.

8q24ll区与瓜德罗普岛（法属西印度群岛）的非洲裔加勒比男性前列腺癌进展的风险相关

Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer （odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P= 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P= 0.001, respectively）. Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC ＋ AA were associated with a higher risk of a Gleasen score 〉7 at diagnosis （OR = 1.79, 95% CI = 1.17-2.73, P= 0.007）. In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.

Influence of functional polymorphism in MIF promoter on sudden cardiac death in Chinese populations

Sudden cardiac death(SCD)is defined as an unexpected natural death without any obvious non-cardiac causes that occurs within 1 h with witnessed symptom onset or within 24 h without witnessed symptom onset.Genetic studies conducted during the past decade have markedly illuminated the genetic basis of the cardiac disorders associated with SCD.Macrophage migration inhibitory factor(MIF)is an upstream immunoregulatory cytokine associated with the pathogenesis of many inflammatory diseases including atherosclerosis and myocardial infarction.Previous studies have reported that the functional -794(CATT)_(5-8) polymorphism in MIF is unrelated to sudden infant deth syndrome susceptibility.However,there are no reports concerning the association between the polymorphism and adult SCD susceptibility.In the current study,we investigated the association between the-794(CATT)_(5-8) polymorphism and adult SCD susceptibility using 79 adult SCD cases and 313 healthy controls.All samples were analysed using a conventional polymerase chain reaction(PCR)technique.We found that CATT_(6) and 5-6 were the most common allele and genotype in both groups,respectively,while no significant association was found between the-794(CATT)_(5-8) polymorphism and SCD susceptibility.We also summarized the allele frequencies of 794(CATT)_(5-8) in cohorts of healthy people from different countries and found that the allele frequency distributions of the polymorphism in Chinese populations were quite different from that of American and European populations(P=0.005,P=0.0001,respectively),but similar to Japanese populations(P=0.827).In conclusion,this study indicates that the-794(CATT)_(5-8) polymorphism may not be associated with adult SCD susceptibility in Chinese populations.Different allele frequency distributions of the polymorphism in multiple populations may provide a useful reference for further genetic association studies.