Association of Q223R Leptin Receptor Gene Polymorphism with Obesity and Type 2 Diabetes Mellitus

The Leptin receptor gene mutation is thought to be associated with an impaired signaling capacity of the leptin receptors, making it a possible candidate gene in the aetiopathogenesis of obesity and diabetes mellitus (DM). However, available reports on the role of LEPR Q223R gene polymorphism in the development of obesity and DM still require further evaluation in African populations. This present study aims to determine the distribution and prevalence of the LEPR Q223R genotype and its allelic frequencies, and possible association with diabetes mellitus among populations in Lagos, South-West, Nigeria.Consenting adults with clinically established DM (n=120) were recruited for this study over a period of six (6) months from the diabetic clinic, and matched for age and sex with apparently healthy controls (n=120). Interviewer-administered questionnaires were used to obtain information on baseline characteristics, demographic data and relevant medical history.  Five milliliters of venous blood were collected for DNA extraction and subsequent PCR amplification and restriction enzyme digestion of amplicon using Msp1.Results show that the genotype frequencies for homozygous wild type (QQ) LEPR 223 SNP (20%); Heterozygous(QR) LEPR SNP (41.7%) and homozygous mutant (RR) recessive LEPR SNP (38.3%) in the study group, were similar to 13.3%; 60% and 26.7% for LEPR 223 QQ, QR and RR genotypes for control group respectively (χ2=4.080; p=0.133). The homozygous (QQ vs RR) and recessive (RR vs QR+QQ) study models showed no significant association with occurrence of DM in the study group (p>0.05). LEPR Q223R SNP was significantly associated with age of onset of DM (OR=2.111), complications of DM (OR=1.934), family history of DM (OR=2.127) and BMI (OR=2.028) among study group participants in a logistic regression model (p<0.05 respectively).We conclude that Leptin receptor gene polymorphism is significantly associated with risk of obesity, predisposition to diabetes mellitus related complications and early onset of DM among Nigerians.  Key words: Leptin receptor; gene polymorphism; Obesity; Diabetes Mellitu