Association of leptin gene polymorphism with obesity

Obesity is a multifactorial disorder with a high morbidity rate worldwide and is associated with various diseases. Certain mutations in the leptin receptor (LEPR) gene may cause splicing abnormality resulting in a truncated receptor, aberrant signal transduction, leptin resistance, and obesity. A cross-sectional analysis was performed to assess the association of Q223R, K109R, and K656N polymorphisms with obesity and overweight in 293 subjects (obesity n= 136, overweight n=44 and controls = 113) belonging to the rural population of Chennai using PCR-RFLP and in silico analysis. The analysis of Q223R in of leptin gene showed a significant association with obesity and overweight individuals when compared with controls (P<0.05). In obesity, heterozygote genotype showed correlation (OR=0.53, p-value=0.03), demonstrating risk association in the study groups. Also, a significant association was observed in the overweight group having a heterozygous genotype (OR=0.32 p-value=0.005). Analysis of K109R showed no association between obesity and overweight (OR=1.18 in obesity, p-value=.0.368, OR=1.02 p=0.575 in overweight). K656N showed a significant association in overweight individuals (OR=2.34, p-value = 0.0162) and no association with obesity (OR= 2.81, p-value 0.075). The functional impact prediction resulted in typing all the alterations not to be damaging or deleterious, with K656N alone predicted to influence the functioning of the protein. The structural impact prediction showed that all the alterations have a destabilizing effect on the resultant protein. The study showed that Q223R is associated with obesity and overweight. K109R showed no association with obesity and overweight. K656N was significantly associated with overweight but showed no association with obesity. However, scale-up studies from ethnic populations related to more than one risk factor could accomplish obesity pathogenesis.