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Single-nucleotide Polymorphism In The 5' Proximal Promoter Of The APN Gene Contributes To The Genetic Risk For Type 2 Diabetes Subjects

Posted on:2005-03-21Degree:MasterType:Thesis
Country:ChinaCandidate:H Y ZhaoFull Text:PDF
GTID:2144360125962729Subject:Internal Medicine
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Dyslipidemia and insulin resistance is closely related to type 2 diabetes mellitus. Therefore, type 2 diabetes mellitus is one of the most common risk factors in the development of coronary heart disease. Besides the factor of environment, genetic factor was found to be one of the contributing causes. Adiponectin, an adipocyte-secreted protein, constitutes of 244 amino acids similar to complement C1q. Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Animal study showed adiponectin can protect against arteriosclerosis,enhance FFA oxidation, antagonize the effects of tumor necrosis factor (, and increase insulin resistance. High-level adiponectin might be a protecting factor against the occurrence of type 2 diabetes. Studies found that APN gene polymorphism could affected lipid metabolism and be associated with type 2 diabetes mellitus. Early studies mostly concentrated in the relationship between the mutations of APN gene's coding region and the level of APN and morbidity of type 2 diabetes. Claudia et al had already reported the T→G exchange in nucleotide 45 and the G→T exchange in nucleotide 276 of the adiponectin gene in Caucasian subjects was associated with insulin resistance. The mutation or miss sense of the coding gene of the APN could result in the hypo-adiponectinemia and the metabolic syndrome related to obesity. The nucleotides located in the proximal promoter would affect the expression of gene, so controlled the variations of the gene may have the relationship with the occurrence of the diabetes mellitus. The mutations in the proximal promoter attract men. Comuzzie et al reported that single-nucleotide polymorphism of-11377C/G and -11391G/A in the 5 proximal promoter of the APN gene showed a strong heritability for plasma adiponectin levels. Froguel found the variation SNP -11377 and -11391 located in the APN proximal promoter are related to high morbidity of 2 type diabetes (p=0.005) and low adiponectin level in French Caucasian subjects in 2002. It is still not clear if it is true in Chinese.Objective: To study the frequency of the variation of single-nucleotide polymorphisms -11377 and -11391 in the 5 proximal promoter of the APN gene in Chinese and to analyses the association of the gene variation with type 2 diabetes, arteriosclerosis complication and dyslipidemia.Methods: 200 were type 2 diabetes (According to WHO 1999 criteria, 103 men and 97 women) with average age of 58.49±13.91 years and 90 nondiabetes normal controls (without T2DM family history and other endocrine disease, 60 men and 30 women, the level of blood glucose were less than 6.0 mmol/L,) with average age of 61.05±10.38 years were enlisted. Genotyping of APN SNP –11377 and -11391 were undertaken with PCR-RFLP method. Height, weight were measured. Levels of blood lipid, glucose were determined with enzymatic method. Serum insulin was determined with RIA (radioimmunoassay) and C peptide was analysed with IRMA (immunoreactive metric assay). Results: The frequencies of CC, CG and GG genotypes of ANP SNP-11377 in nondiabetes groups were 0.74, 0.21, and 0.044, respectively; the allelic frequencies for C was 0.85 and G 0.15. The frequency of CC, CG, and GG genotypes in T2DM were 0.74, 0.185, and 0.075; the allelic frequency of C was 0.8325 and G 0.1675. The frequencies of ANP SNP-11377 genotype and allele din not differ between subjects with T2DM and nondiabetes (χ2=1.105, P>0.05; χ2=0.149, P>0.05). The frequencies of CC, CG and GG genotypes of ANP SNP-11377 in DM with arteriosclerosis groups were 0.76, 0.16, 0.08, respectively, allelic frequencies for C was 0.84 and G 0.16. The frequencies of CC,CG and GG genotypes in DM with no arteriosclerosis were 0.72,0.21, and 0.07, allelic frequencies for C was 0.83 and G 0.17; There were also no differences in genotype and frequencies between DM with arteriosclerosis and DM with no arteriosclerosis (χ2=0.926, P>0.050; χ2=0.036, P>0.050). The frequencie...
Keywords/Search Tags:Type 2 diabetes mellitus, Adiponectin, Polymorphism/Genetics
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