Genetic susceptibility of Iraqis for obesity and type 2 diabetes: LEPR gene polymorphisms

Abstract

Prevalence of obesity and diabetes over world encouraged researchers to expand their studies about genetic predisposition factors which increase individuals' risk for diseases. LEPR gene encodes for leptin receptor which regulates body weight, energy expenditure and insulin sensitivity by binding with adipose derived hormone (leptin). Therefore we sequenced LEPR's promoter, coding exons, exon-intron boundaries and 3′UTRin 45 Iraqi individuals (24 were diagnosed with type 2 diabetes and 21 were not). Seventeen polymorphisms have been detected in this study, 6 in promoter region, 5 in coding exons, 5 in introns (2 were novel) and I Ins/Del in 3′UTR. Type 2 diabetic carriers of rs1137101 in exon 6 were 75% in comparison to non-diabetics (52.4%). Also 50% and 33.3% from diabetic patients and non-diabetics, respectively were carrying p.S343S in exon 9. GC allele in exon 14 increased the BMI of diabetics to 34.6 ± 7.8 but it was 32.4 ± 4.4 in patients with GG allele and both of them were higher in type 2 diabetics than other group (30.2 ± 5.2 and 29.9 ± 2.5, respectively). BMI of diabetic patients with AA allele (P1019P) in exon 20 was 35.7 ± 4 but it was 32.7 ± 5.9 in patients with GG allele, the same was in non-diabetics which was 33.3 ± 4 and 30 ± 3.7, respectively. Also CTTTA insertion allele increased the BMI of diabetics to 35.7 ± 4 in comparison to CTTTA deletion allele as well as 33.3 ± 4 and 29.6 ± 3.5 in other group, respectively. We have concluded that LEPR polymorphisms may increase the risk of developing type 2 diabetes in individuals with BMI ≥ 30 and in general LEPR is a candidate gene for susceptibility to obesity and its outcomes.