Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene, and traits related to obesity in Mexican adolescents

Abstract

Polymorphisms of leptin receptor (LEPR) may contribute to a common form of obesity and, as a consequence, obesity-related diseases. We evaluated the potential role of genetic variation at the LEPR gene in heart sympathetic activity and other traits related to obesity in Mexican adolescents. Adolescents aged between 12 and 17 years, with steady body weight for the last 3 months were included. We evaluated anthropometric measurements, blood pressure, seric glucose, insulin, leptin levels, heart sympathetic activity (by electrocardiograph monitoring at rest), and the Gln223Arg and Pro1019Pro LEPR polymorphisms in each subject. In total, 103 adolescents (55 obese and 48 nonobese) were included. The group of obese adolescents showed higher sympathetic activity, blood pressure, glucose, insulin, and leptin levels. The genotype frequencies for the two polymorphisms were found to be in Hardy-Weinberg equilibrium. There was no difference in the genotype frequencies for Gln223Arg or Pro1019-Pro polymorphisms between obese and nonobese adolescents. However, there was a higher prevalence of Gln223 allele among subjects with higher insulin levels (0.72 vs 0.57; P ¼ 0.04 for adolescents with insulin levels higher and lower than 100 pmol/l, respectively). According to Gln223Arg polymorphism, those with Gln allele (Gln/Gln and Gln/Arg) had higher heart sympathetic activity, body fat percentage, and leptin levels. To conclude, our results support the hypothesis that Gln223Arg polymorphism of LEPR in Mexican adolescents is associated with haemodynamic and metabolic disturbances related to obesity.

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

“…In literature, both alleles of these SNPs have been reported as risk alleles for type 2 diabetes and obesity, and a metaanalytic study reported nonsignificant associations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]48 Consequently, additional studies in larger populations need to be carried out, to verify the involvement of these coding LEPR SNPs in the 'fetal insulin hypothesis'.…”

“…In this study we therefore examined the effect of common SNPs in LEP and LEPR on birth weight and adult metabolic risk factors for type 2 diabetes measured in young twins recruited from the East Flanders Prospective Twin Survey (EFPTS). The SNPs studied have previously been associated with type 2 diabetesrelated traits in other populations, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and are either nonsynonymous or located in a region that might be of importance in the regulation of gene expression.…”

Leptin-Receptor Polymorphisms Relate to Obesity through Blunted Leptin-Mediated Sympathetic Nerve Activation in a Caucasian Male Population

“…However, there have been few investigations on the concurrent relationships between leptin-receptor polymorphisms, plasma leptin levels and sympathetic nerve activity (15). In the present study, three leptin-receptor polymorphisms (Lys109Arg in exon 4, Gln223Arg in exon 6, and Lys656Asn in exon 14) from buffy coats (white blood cells) that may contribute to obesity (11)(12)(13)(14) were studied in a Caucasian male population with a wide range of body mass indices (BMI).…”

Hypertension and genes: perspectives from this journal

“…17 This could potentially lead to the development of new drugs that could target both hypertension and the metabolic syndrome. 18 Also, Guizar-Mendoza et al 19 performed a study to establish the relationship between Gln223Arg polymorphism in the human leptin receptor gene (LEPR) and traits related to obesity in Mexican adolescents. Their study showed that obese adolescents have higher heart sympathetic activity, blood pressure, insulin and leptin levels than non-obese subjects, and furthermore those who were carriers of the Gln223Arg polymorphism of LEPR have sympathetic overactivity and hypertension.…”