Genetic variants in leptin: Determinants of obesity and leptin levels in South Indian population.

The revelation of leptin action mechanisms has led to various attempts to establish the association of polymorphisms in the leptin gene with obesity-related phenotypes. But, outcomes have been contradicting, which made the information on the role of the leptin gene in regulating the mechanism of pathophysiology of obesity inexplicable. Moreover, none of the studies are known to have similar implications on the Indian population. To address such contradictions, our study aims to evaluate the association of leptin gene polymorphism with obesity and leptin levels in a South Indian Population. A total of 304 cases (BMI≥27.5) and 309 controls (BMI≤23) from local inhabitants of Mysore, Karnataka were recruited for the study. The leptin gene variants rs7799039, rs2167270 and rs4731426 independently, as well as in 4 haplotype combinations, were found to be significantly associated with the risk of obesity. An increasing trend in BMI and leptin levels was observed with every addition of A and C minor alleles of exonic variant (rs2167270) and intronic variant (rs4731426) respectively. However, only AA genotype of SNP rs7799039 was positively associated with BMI. None of the SNPs were associated with fat percentage and waist to hip ratio. On a whole, this data suggests that the common polymorphisms in the leptin gene are strong predictors of obesity and leptin levels in South Indians.

MTNR1B gene polymorphisms and susceptibility to Type 2 Diabetes: A pilot study in South Indians.

Type 2 Diabetes (T2D) is the major health concern in the Indian subcontinent. A genome-wide association study carried out with non-diabetic Indians showed association of MTNR1B variants with fasting glucose. MTNR1B mediates the effect of melatonin on insulin secretion. In light of the growing importance of MTNR1B in the etiology of T2D, we sought to test its association with the disease in the south Indian type 2 diabetics. Five single nucleotide polymorphisms of MTNR1B (rs10830962, rs10830963, rs3847554, rs1387153 and rs2166706) were genotyped in 346 T2D patients and 341 non-diabetic controls. None of the SNPs differed significantly between patients and controls with respect to allele and genotype frequencies. Linear regression analysis after adjustment for age, sex and BMI showed a significant positive association of rs3847554 with fasting glucose under recessive model (ß=14.98, p=0.012). Haplotypes constituted by minor alleles of rs3847554, rs1387153, rs2166706, rs10830963 and major allele of rs10830962 showed significant positive correlation with fasting glucose (p<0.05). Though the results obtained are suggestive of MTNR1B role in T2D etiology, they need to be confirmed with much larger sample sizes.

Menopause versus aging: The predictor of obesity and metabolic aberrations among menopausal women of Karnataka, South India.

CONTEXT: Increased incidences of cardiovascular disorder and metabolic syndrome particularly after menopause have raised curiosity for the underlying factors. However, it is still a debate whether age or menopausal transition is a greater contributor. AIMS: To elucidate the inter-relationships of age, menopause, and associated obesity and to assess their independent effects on aggravation of cardio metabolic risk factors in postmenopausal women. SETTINGS AND DESIGN: Four hundred two women aged between 30 and 75 years were recruited in a cross-sectional study from Southern India. Three hundred sixteen participants exempting exclusion criteria, comprising of 169 premenopausal and 147 postmenopausal women were finally included. MATERIALS AND METHODS: Anthropometric measurements such as weight, height, waist circumference (WC), hip circumference (HC), fat percentage, basal metabolic rate (BMR), and blood pressure were taken. Fasting plasma glucose, postprandial glucose, glycated hemoglobin (HbA1c), lipid profile, and C-reactive protein (CRP) were also measured. STATISTICAL ANALYSIS USED: Independent t-test, Analysis of covariates (ANCOVA), Pearson's correlation coefficients and multiple stepwise linear regression model analysis were done. RESULTS: A significant increase in physical and metabolic factors was observed in postmenopausal women compared to premenopausal women except WC and HbA1c. Contrastingly, high-density lipoprotein cholesterol (HDL) levels and BMR were significantly decreased. After adjusting for BMI and age, the significant differences in the variables through the menopausal transition persisted, including an increase in WC. Significant correlation was observed between age and measures of general obesity such as BMI (P < 0.05) and fat percentage (P < 0.001) but not with central obesity indices. Menopausal status and WC exerted an independent effect on most of the metabolic risk factors (P < 0.001 or P < 0.01). Fat percentage was the predicting variable for CRP, HbA1c, diastolic blood pressure (P < 0.001), and HDL (P < 0.01). But Age showed independent effect only on HbA1c. CONCLUSIONS: Menopausal transition brings about anomalies in total body composition characterized by an increased body fat mass and central adiposity. This creates a compatible atmosphere for abnormal metabolism and aggravated cardio metabolic risk factors. Thus, menopausal status and associated obesity is the major predictor of metabolic aberrations over age in menopausal women.