| Objective: This research is aimed to investigate the association between the five single nucleotide polymorphism of four genes(rs679899 of APOB gene,rs6078 and rs6083 of LIPC gene,rs3826810 of LDLR gene,rs3798220 of LPA gene)and type 2 diabetes in Guangxi region,which join the pathways of lipid digestion,mobilization and transport.Methods: A case-control study was conducted in 929 patients with type 2diabetes and 1044 healthy controls.The peripheral venous blood from each subjects was collected to extract DNA by qiagen method.Five SNPs(rs679899,rs6078,rs6083,rs3826810,rs3798220)were genotyped in the method of Matrix-assisted laser desorption ionization time-of-flight mass spectrometry technology(MALDI-TOF-MS).Group t test and F test were used for measurement data and Chi square test was used for categorical data.The plink software was utilized to analyze Hardy-Weinberg genetic equilibrium and SNPs allele frequency and genotype analysis.Multifactor dimensionality reduction(MDR)was applied to construct the interaction between different SNPs.The model of unconditional logistic regression was used to analyze gene-environment interaction.All of above tests were performed using two-sided test,test level ? = 0.05.Results:(1)General demographic characteristics: After excluding 76 samples,890 patients with type 2 diabetes and 1007 health subjects were included inplink software calculation.The average age was 64.79±10.03 in the case group and 64.02±9.49 in the control group.There was a significance difference between two groups in drinking,BMI,TC,TG and HDL(P<0.05).(2)Analysis of the association between different SNPs and type 2 diabetes:The distributions of 5 SNPs in the control group was consistent with the hardy-Weinberg equilibrium in this study(P > 0.05).Comparing with the case group,the allele distribution of rs679899 on APOB gene was statistically significance in the control group(P < 0.05).In the co-dominant model,the distribution of CC genotype and TT genotype was statistically siginificant between the case group and control group on rs3798220 on LPA gene in female(P < 0.05).Similarly,in recessive model,the distribution of TT+CT genotype and CC genotype was statistically siginificant between the case group and control group(P<0.05).(3)Interaction analysis: In the analysis of MDR software,the results showed that there might be gene-gene interaction among four sites—rs679899,rs3798220,rs6078,rs6083(P < 0.05).We did not find a gene-environment interaction in the logistic regression model.(4)haplotype analysis: Haplotype analysis by haploview4.2 software did not reveal a statistically significant haplotype(P>0.05).(5)Analysis of different SNPs and lipid metabolism in serum: In the case group,there was a connection between the polymorphism of rs6078 on the LIPC gene and the level of LDL,HDL and TC in serum;rs6083 on the LIPC gene was associated with the level of TC;rs3798220 on the LPA gene was related to the level of TG(P<0.05).In the control group,rs3798220 on the LPA gene was found to associated with the level of TC(P<0.05).Conclusions:(1)In female,the CC genotype of rs3798220 on the LPA genemight be a susceptible genotype of type 2 diabetes.(2)There may be gene gene interaction between the four SNPs(rs679899,rs3798220,rs6078,rs6083).(3)The results showed that GA genotype of rs6078 on LIPC gene may be associated with the high expression of the LDL,HDL and TC in serum of T2 DM patients.Likewise,the A allele was related to the high expression of HDL and TC in serum of T2 DM patients.(4)AA genotype of rs6083 on LIPC gene might be associated with the elevated serum TC of T2 DM patients.(5)There might be association bewteen GG genotype of rs3826810 on LDLR gene and the elevated serum TG of T2 DM patients.(6)We found that there was a possible association bewteen TT genotype of rs3798220 on LPA gene and the elevated serum TG of T2 DM patients. |
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