Polymorphisms in the leptin receptor (LEPR)--putative association with obesity and T2DM.
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 > 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.
Park
Kyong Soo
KS
Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, 110-744, Seoul, Korea.
Shin
Hyoung Doo
HD
Department of Genetic Epidemiology, SNP Genetics, Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, 153-803, Seoul, Korea.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, 153-803, Seoul, Korea.
Cheong
Hyun Sub
HS
Department of Genetic Epidemiology, SNP Genetics, Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, 153-803, Seoul, Korea.
Cho
Young Min
YM
Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, 110-744, Seoul, Korea.
Lee
Hong Kyu
HK
Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, 110-744, Seoul, Korea.
Lee
Jong-Young
JY
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, 122-701, Seoul, Korea.
Lee
Jong-Keuk
JK
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, 122-701, Seoul, Korea.
Oh
Bermseok
B
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, 122-701, Seoul, Korea.
Kimm
Kuchan
K
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, 122-701, Seoul, Korea. k2kimm2@nih.go.kr.
D000368:Aged; D001483:Base Sequence; D015992:Body Mass Index; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D012044:Regression Analysis; D017422:Sequence Analysis, DNA
C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin