Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians

Abstract

Background : Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. However, the findings have been inconsistent due to high level of confounding. In this study, we aim to examine the association of omentin gene polymorphism with plasma adiponectin levels and cardiometabolic health status using a genetic approach, which is less prone to confounding, and investigate whether these associations are modified by lifestyle factors such as diet and physical activity. Methods : The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were further classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The A326T (rs2274907) single nucleotide polymorphism (SNP) in the exon 4 of the omentin gene was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Results : The ‘A’ allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p=1.90 x 10 -47 ). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p=7.47x10 -10 ). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of ‘A’ allele with cardiometabolic health status disappeared (p=0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). Conclusions : Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in this Asian Indian population. Further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases.

GeNuIne (gene–nutrient interactions) Collaboration: towards implementing multi-ethnic population-based nutrigenetic studies of vitamin B12and D deficiencies and metabolic diseases

“…Several studies have shown that healthy lifestyle may modify the association between genetic risk and metabolic disease-related traits (10)(11)(12)(13)(14)(15)(16) . Although some studies have shown that increased physical activity levels and healthy diet can attenuate the effect of genetic variants on metabolic traits, other studies have shown conflicting results (17) , which could be attributed to genetic heterogeneity and differences in the dietary patterns across multiple ethnic groups (7,18,19) .…”