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Association Of Adiponectin Gene, Tumor Necrosis Factor-α Gene Polymorphisms And Serum Levels With Type 2 Diabetes

Posted on:2007-04-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y L WeiFull Text:PDF
GTID:2144360215489561Subject:Genetics
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Obstract: To clarify the susceptible genes associated with type 2 diabetes millutes(T2DM) in the Han nationality population of Ningxia. We detected two candidate genes polymorphims those have been confirmed the association with T2DM in other population. Inorder to ascertain the association of the two candidate genes with T2DM in the Han nationality population of Ningxia and to investigate into the interactions between those candidate gene polymorphisms in the Han nationality of Ningxia T2DM.The two candidate genes polymorphisms include the SNP45 polymorphisms in adiponectin gene, the SNP-308 polymorphisms in the Tumor necrosis factor-αgene. To study the relationship of the adiponectin+45nucleotide T/G polymorphism to insulin resistance , obesity and T2DM. and study the relationship of the polymorphism to serum adiponectin level.To investigate the relationships between serum adiponectin levels, Tumor necrosis factor-α(TNF-α), body mass index(BMI), insulin sensibitity and some related factors, elucidate the role and mechanisms of these factors in development of type 2 diseases.Methods: The information of study subjects were collected according to the criterions, including height,weight,fasting blood glucose (FBG),lipids,Ins, etc;We studied 100 unrelated random subjects with T2DM (cases) and 101 non-diabetes (controls) those were selected from the Han nationality population of Ningxia. The polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) analysis were used to tested the distribution of allele and genotype frequencies of the two gene polymorphisms in two groups of the Han nationality population of Ningxia. To calculate the association between the gene polymorphisms and T2DM using population genetics methods in the Han nationality population of Ningxia ; By using radioimmunoassay (RIA) and enzyme linked immunosorbent assay(ELISA) methods, the fasting levels of serum adiponectin and TNF-αare remeasured in 101 healthy subjects,100 patients with T2DM. fasting seruminsulin(FINS) was reassayed simultaneously.Results: The frequency of alleles of two genes reached the Hardy-Weinberg equilibrium, this shows that the population studied were selected randomly. BMI, the levels of FBG, FINS, TC, TG, LDL-C etc were significantly higher in T2DM group than in normal control group (P<0.01); The serum adiponectin levels, HDL-C and SI were significantly lower in T2DM group than in normal control group(P<0.01). There was no significant difference in the levels of TNF-αbetween T2DM group and normal control group(P>0.05). The distribution of genotype and allele frequencies of the SNP45 polymorphism were different in diabetes and control groups(P<0.01)). The frequency of G allele in type 2 diabetic group was higher than that in normal controls(P<0.01). The frequency of T allele in type 2 diabetic group was lower than that in normal controls(P <0.01) But no assiciations were found for the polymorphisms in the genes for TNF-αgene; The BMI of TG+GG genotypes of adiponectin in the type 2 diabetic group was higher than that of TT genotype(P<0.01). The BMI of each genotype of adiponectin in normal controls had no significant difference. The frequencies of TG+GG genotypes and G allele in BMI≥25 subgroup of the type 2 diabetic group were higher than those in BMI<25 subgroup(P <0.01); The HOMA-IR of TG+GG genotypes of adiponectin in in the type 2 diabetic group was higher than that of TT genotype(P<0.05), which was still significant after correction with BMI. The HOMA-IR of each genotype in normal controls had no significant difference; The serum adiponectin of T/G+G/G genotypes in the type 2 diabetic group was lower than that of T/T genotype(P<0.01). The serum adiponectin levels were positively correlated with SI(P< 0.05), and negatively correlates with BMI (P<0.05), and no correlates with TNF-α(P>0.05).Conclusions: These results suggest that the SNP45 polymorphism in adiponectin gene has close relation with T2DM in the the Han nationality population of Ningxia; The SNP-308 polymorphism in TNF-αgene has not close association with T2DM in thethe Han nationality population of Ningxia. The polymorphism of adiponectin +45 nucleotide T/G was associated with obesity , insulin resistance and serum adiponectin level, and the adiponectin gene maybe a new susceptibility gene to T2DM. The serum adiponectin levels were correlated with BMI, no correlates with TNF-α.
Keywords/Search Tags:adiponectin, TNF-α, gene polymorphism, T2DM
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