Association Study Of GIP And GIPR Gene Polymorphism With Abdominal Obesity And Metabolic Syndrome

Background and Aim:Glucose-dependent insulinotropic polypeptide (GIP), a gastrointestinal hormone, acts directly on adipose tissue, promotes lipid deposition and leads to obesity via its receptor-GIPR. GIP and GIPR are interesting candidate genes for obesity, lipid metabolism and metabolic syndrome. We aimed to reveal the association between common variants in GIP and GIPR genes with obesity and metabolic syndrome among Chinese Han population.Methods:500natural population subjects and236cases with diabetes were enrolled. The definition and criteria of metabolic syndrome used in this study matched those proposed International Diabetes Federation (IDF) in2005. Genotyping single nucleotide polymorphisms (SNPs) in GIP (rs2291726) and GIPR (rs1800437, rs2302382) were performed by ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) and PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Sequencing was performed after PCR to identify the results. We conducted two follow-up of natural populations and analyzed the predictive value of GIP and GIPR genotype for new onset metabolic syndrome and its components. Statistical analysis was carried out by the software SPSS20.0.Results:Of500natural population subjects,66(13.2%)fulfilled the IDF criteria for metabolic syndrome. Of236patients with type2diabetes,145(61.4%) fulfilled the IDF criteria for metabolic syndrome. Logistic regression analysis showed a significant association of all three SNPs with abdominal obesity (waistline male≥90cm, female>80cm) after adjusting for age and gender. In natural population group, additive and recessive model at rs2291726, OR were2.19(P=0.022) and2.03(P=0.028); in additive and dominant model at rs2302382, OR were1.97(P=0.007) and1.92(P=0.008). In diabetic group, additive, dominant and recessive model at rs1800437, OR were6.54,4.01and4.6, P value were0.009,0.038and0.021, respectively. In natural population group, rs2291726were significantly associated with obesity (BMI≥28; OR6.35, additive model, P=0.004; OR3.14, dominant model, P=0.029; OR3.85, recessive model, P=0.009). Rs2291726was associated with metabolic syndrome in natural population group (OR3.65, P=0.001, additive model; OR1.73, P=0.048; dominant model; OR3.13, P=0.002, recessive model). Rs1800437was associated with metabolic syndrome in diabetic group (OR4.67P=0.03, additive model; OR3.77, P=0.044, dominant model). In natural population, after adjusted for age and gender, the risk alleles at three SNPs increased the risk of developing high total cholesterol at rs1800437, high LDLc at rs2302382. We find no associations between genotype and new onset metabolic syndrome and its components in the follow-up data. Conclusions:Our data indicate that GIP and GIPR gene polymorphism are risk factors for abdominal obesity and metabolic syndrome in Chinese Han population. This provides new insight for the prevention and treatment of obesity and metabolic syndrome.