| According to the investigation of chronic diseases in China in 2010, the adult overweight rate was 30.6% and the obesity rate was 12.0%, obesity has become one of the most common chronic metabolic diseases. Obesity is the major risk factor for high blood pressure, diabetes, coronary heart disease and some malignant tumors. It is one of the major public health problems. In recent years, studies have found that PRDM16(positive regulatory domain containing 16,PRDM16) can affect the body’s metabolism and energy consumption through adjusting the differentiation of brown adipose tissue, it plays a potential role in fighting against obesity. Epigenetic changes can also lead to change of the phenotype. The methylation level of the promoter sequence is closely related to obesity.Objective To evaluate whether PRDM16 gene polymorphisms and promoter region methylation level might be associated with the development of overweight or obese, and to explore the molecular mechanism of overweight and obesity from the way of classic genetics and epigenetics.Methods⑴The study of gene polymorphisms: A field investigation was carried out in 2011, using cluster random sampling in some county in the city of Luoyang in Henan province to select five villages. The investigation totally surveyed 583 people and 528 people were left eliminating the blood relationship within three generations. The subject can be divided into two groups according to the BMI: The overweight and obesity group(BMI≥24 kg/m2) and the normal weight group(18.5kg/m2≤BMI<24 kg/m2).The polymorphism of rs2236518 in PRDM16 gene was genotyped by the method of snapshot. The polymorphisms of rs2651899, rs2282198, and rs870171 were genotyped by the method of ligase detection reaction(LDR).⑵The study of methylation level: Collect 116 samples based on the hospital. The subject can bedivided into two groups according to the BMI: The overweight and obesity group(BMI≥24 kg/m2) and the normal weight group(18.5kg/m2≤BMI﹤24kg/m2). Use mass spectrometry methylation method to detect the methylation level of promoter region in PRDM16 gene.Data was analyzed by IBM SPSS 21.0 software. Hardy-Weinberg equilibrium for each SNP was tested by chi-square test. Distribution of genotype and allele frequency between the two groups were compared by contingency table chi-square test. Haplotype analyses were conducted through the SHEsis online software. Distribution differences between different groups of the methylation level were performed by t test. Multiple linear regression was used to analysis the methylation level of each Cp G with the BMI. The significant level of statistical analyses above was 0.05.Results⑴There was significant difference of rs2651899 in frequency of allele G between the two groups(OR(95%CI)=0.765(0.599~0.979),P=0.033).⑵Haplotype analysis showed significant differences in frequency of haplotype ACAA, ACCA, ATCA, GTAA, GCCA, GCCC between two groups.(ACAA:OR(95%CI)=2.004(1.006~3.992),P=0.044;ACCA:OR(95%CI)=0.581(0.345~0.979),P=0.039;ATCA:OR(95%CI)=1.867(1.252~2.784),P=0.002;GTAA:OR(95%C I)=0.327(0.132~0.807),P=0.011;GCCA:OR(95%CI)=0.428(0.223~0.824),P=0.009;G CCC:OR(95%CI)=2.505(1.135~5.528),P=0.019).⑶There was no significant difference between two groups of the twelve CpG sites in the promoter region.The correlation coefficients of Cp G sites with BMI have no statistical significance.Conclusion Allele G of rs2651899, haplotypes ACCA, GTAA and GCCA may be protective factors to overweight and obesity, haplotypes ACAA, ATCA and GCCC may be risk factors of genetic susceptibility to overweight and obesity.The methylation status of promoter region of PRDM16 gene has no effect with the overweight or obesity. |
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