Association analysis of Leptin melanocortin signaling pathway genes with diabetes and obesity

Abstract

Type 2 diabetes (T2DM) and obesity are complex disorders that constitute major public health problems. The evidence for familial aggregation of both T2DM and obesity is substantial. To date, more than 150 genetic loci are associated with the development of monogenic, syndromic, or multifactorial forms of T2DM or obesity. However, the proportion of overall trait variance explained by these associated loci is modest (~5 10% for T2DM, ~2% for body mass index (BMI). Some of the familial aggregation not attributable to known genetic variation, as well as many of the effects of environmental exposures, may reflect epigenetic processes. Identification of genes involved in the progression of these diseases is largely hampered by challenges inherent in mapping genes due to high prevalence, genetic heterogeneity and wide clinical spectrum. Environmental and genetic factors together are attributed to explain the spectrum of geographical and population dependent variations in the incidence of these complex diseases. Incidentally researchers have come up with controversial results with regard to the association of diabetes and obesity despite a varied spectrum of polymorphic changes reported in the genes harboured by the locus. The controversy is largely attributed to population heterogeneity. The purity of genetic traits associated with Kashmiri population is likely to minimize the influence of mixed risk/resistance alleles to reliably establish their potential association. newlineThe SNP observed in codon 251 of melanocortin-4-receeptor (MC4R) gene (Ile251Leu) showed a significant difference between patients and control subjects (p genotypeand#8804;0.001, p alleleand#8804;0.001). Association was also found significant with BMI, fasting blood sugar (FBS), postprandial blood sugar (PPBS), random sugar (RS), total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL) and waist to hip ratio (WHR) (p=lt0.05) in this polymorphism. But parameters like age and high density lipoproteins (HDL) did not differ between controls and cases........