Association Analyses Of Adiponectin Gene Single Nucleotide Polymorphisms With Type 2 Diabetes In Han Chinese In Hubei

Type 2 diabetes mellitus(T2DM)is complex disease characterized by elevated blood glucose level that results from insulin resistance and deficiency inβcell secretion.Genetic factor plays a crucial role in the development of T2DM.In the diabetes pathological process,carbohydrate,protein and lipid metabolism have been disordered. Adiponectin(APM1)is adipocyte-derived plasma protein,which is one of the most abundant and unique protein expressed in adipose tissue.It plays an important role in the regulation of glucose and lipid metabolism.Plasma APM1 levels have been reported to be reduced in patients with T2DM,obesity and coronary heart disease,all of which are closely related to insulin resistance.The APM1 gene is localized to human chromosome 3q27,where the T2DM and MS susceptibility locus was identified in genome-wide scans.Therefore,APM1 gene is a good candidate gene of T2DM.To investigate the association between the APM1 gene single nucleotide polymorphisms rsl3061862(SNP45)and rs1501299(SNP276)and T2DM,a total of 603 Han Chinese subjects including cases and controls from Hubei province were genotyped by PCR-RFLP and PCR-SSCP.Both family-based case-control and unrelated case-control designs were used.Association analysis is tested byχ~2 and logistic regression.Haplotype analysis is conducted in haploview3.23.(1)The frequencies of the G allele and GG genotype for T2DM patients were significantly higher than those for controls(G:42.0%vs21.7%,P＜0.001;GG: 13.6%vs4.5%,p＜0.001,OR=3.298,95%CI=1.678-6.482)in all subjects;The GG genotype was associated with higher risk of T2DM in 180 family-based case-control groups(GG:17.8%vs5.6%,P=0.011),while the G allele and GG genotype for T2DM patients were significantly higher than those for controls in the 423 unrelated case-control groups(GG:12.2%vs3.9%,P=0.002);Logistic regression analysis suggested that GG genotype was the genetic risk factors for T2DM(OR=3.58, 95%CI=1.70-7.54).In conclusion,the APM1 SNP 45T/G is associated with T2DM risk, and the GG genotype may be a genetic risk factor of T2DM in Han Chinese population of Hubei.(2)The frequencies of the T allele and TT genotype for T2DM patients were significantly higher than those for controls(T:39.1%vs30.4%,/9=0.008;TT:20.2% vs14.0%,p＜0.001,OR=2.326,95%CI=1.463-3.697)in all subjects.Logistic regression analysis suggested that TT genotype was the genetic risk factors for T2DM(OR=2.904, 95%CI=1.734-4.864).Multivariate logistic regression indicated that FPG(p＜0.001)and SNP276(P=0.01)genotype were independent risk factors of T2DM.In conclusion,the APM1 SNP276G/T is associated with T2DM risk,and the TT genotype may be a genetic risk factor of T2DM in Han Chinese population of Hubei.(3)Haplotype analysis indicated that the frequencies of haplotype TG and GT were significantly different in all cases and controls(p＜0.001 and P=0.001).The haplotype TG with higher frequencies in control group(0.479 vs 0.343)was the protective factor of T2DM,where the haplotype GT with higher frequencies in case group(0.187 vs 0.113) was the risk factor of T2DM.(4)In stratified analysis on the basis of sex,the frequencies of SNP45 GG genotype and G allele for T2DM patients were significantly higher than those in controls (genotype:P=0.001;allele:P=0.003)in the male subjects.In stratified analysis on the basis of BMI level,the frequencies of SNP45 GG genotype and G allele for T2DM patients were significantly higher than those in controls(genotype:P=0.002;allele:P= 0.015)in BMI＜23 subjects;the frequencies ofSNP45 G allele for T2DM patients were significantly higher than those in controls(P=0.042)in 23≤BMI≤25 subjects;In stratified analysis on the basis of sex,the frequencies of SNP276 TT genotype and T allele for T2DM patients were significantly higher than those in controls(genotype:P= 0.025(male);P=0.001(female);allele:P=0.030(male);p＜0.001(female))in male and female subjects.In stratified analysis on the basis of BMI level,the frequencies of SNP276 TT genotype and T allele for T2DM patients were significantly higher than those in controls(genotype:P=0.016;allele:P=0.005)in BMI＜23 subjects;the frequencies of SNP276 T allele for T2DM patients were significantly higher than those controls (P=0.033)in BMI＞25 subjects.These results show that a interaction between APM1 gene and sex and BMI exists.In conclusion,the APM1 gene is associated with T2DM and is a susceptibility gene for T2DM in Han Chinese in Hubei province.