Abstract
BACKGROUND: Various genes related to fat-, sugar-or energy-metabolism are suspected that their polymorphisms (SNPs) are susceptible to development of obesity and other metabolic syndromes. Although many lines of evidences are accumulated, inspections as to their relation are still insufficient. Here, we assembled 235 obese people in Saku Control Obesity Program (SCOP), and are going to investigate the association between those SNPs, body mass index (BMI) and other clinical parameters. METHODS: 235 subjects, whose BMI belonged in upper quintile (over 28.3), are recruited from examinees for periodic medical checkup in the Health Dock of Saku Central Hospital (Nagano, Japan). Genotyping for the SNPs were conducted using the PCR-PFLP method from peripheral venous blood. The frequencies of the SNPs in UCP1 (-3826A/G), UCP2 (Ala55Val), UCP3 (-55C/T), PPARγ2 (Pro12Ala), adiponectin (Ile164Thr), leptin receptor (LEPR, Arg109Lys), calpain 10 (SNP43), β2AR (Arg16Gly, Gln27Glu), β3AR (Trp64Arg) were analyzed and associations between those SNPs, body mass index (BMI) and other clinical parameters were investigated. The frequency was compared with those in HapMap Project or in Nansei Cohort.. RESULTS: Frequencies of above SNPs in SCOP were not different from those of healthy people in Nansei Cohort or HapMapProject, except for adiponectin Ile164Thr. SNPs of UCPs or β2, β3AR genes, often reported their association with BMI, were not confirmed in obese subjects in SCOP. We found significant association in the LEPR Arg109Lys in woman; Lys/Lys minor homozygotes had higher levels of leptin, TNF-α, C-peptide, insulin, triglyceride and fasting serum glucose, and also, the genotype showed a trend of higher values of HbA1c, BMI, body fat mass and waist circumference. CONCLUSION: Adipocytokines, such as leptin and adiponectin, may play an important role in the development of metabolic syndrome, and they would be influenced by polymorphism of UCP or β2, β3AR genes.
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