| BackgroudObesity is a multifactorial disease. According to the criteria of the Adult Treatment Panel-III (ATP-III), obesity includes two types, namely metabolically unhealthy obesity (MUHO) and metabolically healthy obesity (MHO). The two types have different features in the etiology and treatment. Hundreds of obesity candidate genes have been found by Genome-Wide Association Study (GWAs), including melanocortin-4 receptor (MC4R). Beside GWAs, research about relationship between obesity and adipocytokines is more and more important. Glypican-4 plays similar roles as insulin by directly binding to insulin receptor, promoting glucose uptake and differation of preadipocytes; irisin, is encoded by fibronectin III type structure domain 5 (FNDC5) gene, and it can convert white fat into brown fat and improve glucose tolerance.ObjectiveThe objective of the study is to investigate whether FNDC5, MC4R, GPC4, GNPDA2 variants are associated with Chinese Han population, to screen out of obesity-related SNPs markers.MethodsThe study population consisted of 1100 healthy Hans who were long-term residents of Beijing. The age is ranging from 18 to 83 years. We conducted a case-control study, erecting four groups of metabolically unhealthy obesity (BMI≥30kg/m2 and ATP-Ⅲ≥2), metabolic healthy obesity(BMI>30kg/m2 and ATP-Ⅲ≤1), metabolic unhealthy non-obesity(BMI< 25kg/m2 and ATP-Ⅲ≥2) and metabolic healthy non-obesity(BMI<25kg/m2 and ATP-Ⅲ<1).A comprehensive SNP selection, including tag SNP, functional SNP and SNP from reference, was applied. Then we choose the suitable SNPs of which the minor allele frequency in Chinese is more than 15%. Genotyping for the selected genetic polymorphisms was performed using Sequenom array.Results"Case-Control" association analysis of MC4R (1) Between the obesity and normal weight group, there were significant differences in the genotypes frequencies of rs2331841 (P=0.039). In logistic regression, the AA genotype obesity risk increase 1.28 fold than that of TT genotype, accounting for 0.9% of obesity etiology. Among three genotypes of rs17782313, rs571312, rs12970134, rs6567160 and rs2331841, there was a significant difference in DBP. (2) Between the obesity and MUNO group, there were significant differences in the alleles frequencies of rs2331841 (P=0.034). (3) Between the MUHO and MUNO group, there were significant differences in the alleles frequencies of rs2331841,rs656710,rs17782313 and rs571312(P=0.005,P=0,001,P=0.015,P=0.013). There were significant differences in the genotypes frequencies of rs2331841, rs656710, rs17782313, rs571312 and rs12970134 (P=0.008,P=0,026,P=0.03, P=0.041, p=0.048). (4)Between the MUHO and MHO group, there were significant differences in the alleles frequencies of rs2331841(P=0.039); there were significant differences in the genotypes frequencies of rs2331841, rs17782313 and rs12970134 (P=0.017, p=0.027, p=0.044). "Case-Control" association analysis of FNDC5, between the MUHO and MUNO group, there were significant differences in the genotypes frequencies of rs16835198 (p=0.050);. Between the MUHO and MHO group, there were significant differences in the alleles frequencies of rs16835198 and rsl746661 (P=0.047, P=0.048). Among three genotypes of rs1746661, there was a significant difference in BMI and weight. Among three genotypes of rs16835198, there was a significant difference in SBP, DBP. The results of LD and R2 of the SNPs indicated rs16835198, rs3480 and rs1746661 belonged to the same block, TAG is the most common inherence type. We found significant difference between obesity and normal weight group (P=0.05)"Case-Control" association analysis of GPC4, between the obesity and MUNO group, there were significant differences in the genotypes frequencies of rs7059265 (p=0.049). Among three genotypes of rs1129880, rs3761628, rs2073288 and rs7059265, there was a difference in SBP, DBP, TG, HDL, BUN, UA and weight. Moreover, between obesity and normal weight group there were significant differences in serum level of glypican 4 (p=0.007).Conclusions1) A risk allele and AA genotype of rs2331841 (MC4R)could increase the risk of obesity. The participants with A risk allele of rs2331841 have a higher risk of MUHO2) The participants with low frequency allele of rs656710, rsl7782313, rs571312 and rs12970134 (MC4R) have a higher risk of MUHO3) The participants with high frequency allele of rs16835198 (FNDC5) and rs7059265 (GPC4) have a higher risk of MUHO... |
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