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Leptin plays an important role in regulating adipose-tissue mass. Leptin controls energy balance and food intake through the leptin receptor in the hypothalamus of the brain, which suggests that some polymorphisms of the leptin receptor gene (LEPR) might contribute to obesity or obesity-related diseases. In an effort to identify genetic polymorphisms in a potential candidate gene for obesity and type 2 diabetes mellitus (T2DM) in the Korean population, we have sequenced the LEPR gene. Thirty-five sequence variants were identified (including 9 novel polymorphisms): 1 single nucleotide polymorphism (SNP) in the promoter region, 1 SNP in the 5' UTR, 8 SNPs in exons (3 non-synonymous SNPs), 23 SNPs in introns, 1 ins/del in the 3' UTR, and 1 SNP in the 3' downstream region. To investigate possible association of LEPR polymorphisms with body mass index (BMI) and the risk of T2DM, we genotyped for 11 polymorphisms in the Korean population (n = 1,463). Using statistical analyses, no significant associations between the genetic polymorphisms in the LEPR gene and the risk of T2DM were detected. However, one non-synonymous SNP in exon 3, +5193G &gt; A (Arg109Lys), showed marginal association with BMI (P = 0.02) and gene dose-dependent genetic effects were observed. The present study provides information about additional genetic polymorphisms in LEPR and positive associations of those polymorphisms with BMI in the Korean population.

Polymorphisms in the leptin receptor (LEPR)—putative association with obesity and T2DM