Identification of genetic basis of obesity and mechanistic link of genes and lipids in Pakistani population.

We aimed to identify the genetic causes of common forms of obesity in the Pakistani people and find out the mechanistic link by observing the relationship of genes and serum lipid traits. Four hundred and seventy-five subjects were genotyped for two mutations in (leptin:N103K and proopiomelanocortin:R236G) and ten common variants in different genes. Serum lipids were also measured. The prevalence of mutations was very low (one heterozygous subject each for both mutations), but fairly high minor/risk allele frequency (M/RAF) was observed for all SNPs. MAF of G2548A was 42.8% in obese and 30.1% in controls (P=5.7 x 10(-5)), it showed association with weight, body mass index (BM!), waist circumference (WC), high density lipoprotein cholesterol (HDL-c) and leptin, Gln223Arg had MAF 32% in obese and 18.7% in controls (P=5.4 x 10(-6)), it showed association with fasting plasma glucose (FPG) and all lipid traits, Ala54Thr had MAF 42.4% in obese and 33.1% (P=0.002), it showed association with none of the tested parameters. rs9939609 MAF was 26.6%, and showed association with none of the tested parameters. rs1802295 (P=0.002); rs7178572 (P=0.007); rs2028299 (P=0.04); rs4812829 (P=0.02) showed significant while rs3923113 and rs16861329 did not show a significant association (P=0.20 and P=0.3, respectively) with obesity. Major genetic contribution to common forms of obesity in Pakistan is from low/modest effect size common variants that act additively to affect body weight quantitatively and mechanism may involve modulating serum lipids.