Impact of Genetic Loci Identified in Genome-Wide Association Studies on Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes.

PURPOSE: Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DR-susceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. METHODS: Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed. RESULTS: The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted= 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models. CONCLUSIONS: We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.

Adiponectin gene variants and the risk of coronary heart disease: a 16-year longitudinal study.

OBJECTIVE: Circulating adiponectin levels have been shown to be associated with a risk of coronary heart disease (CHD). However, its primary role in protecting against the development of CHD remains controversial due to conflicting observations in prospective studies. To gain further insight into the primary role of adiponectin, our major objective was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and incident CHD in a population-based cohort with no CHD at baseline. DESIGN AND METHODS: We conducted a 16-year longitudinal study in 2196 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). During 33 862 person-years of follow-up, 184 subjects developed CHD (cumulative incidence rate=5.4 per 1000 person-years). Nine ADIPOQ SNPs with potential functional relevance or shown to be associated with adiponectin levels and/or CHD were genotyped. RESULTS: Among the nine ADIPOQ SNPs, +276G>T (rs1501299) was independently associated with incident CHD in men but not in women, even after adjustments for traditional cardiovascular risk factors (Padjusted=5.5×10(-3) to 0.023; hazard ratio=1.39-1.54). Furthermore, there was a significant association of the T allele of +276G>T with a lower adiponectin level (P=0.027; ß (95% CI)=-0.05 (-0.10, -0.01). CONCLUSIONS: This study demonstrated that +276G>T may be an independent predictor of CHD development. Our findings suggest that low adiponectin levels, as may be influenced by +276G>T, confer a higher risk of CHD, in keeping with a role of hypoadiponectinaemia in the development of CHD in the general population.