| Objective To study associations among single nucleotide polymorphisms (SNPs) of candidate genes and hypertension, plasma glucose, lipids and insulin resistance phenotypes, we would like to test associations and genotype interactions among candidate gene SNPs and related phenotypes in Chinese Han type2diabetes mellitus (T2DM) patients. Candidate genes were selected based on our previous association studies, biological function, and published genome-wide association studies of T2DM, obesity, and lipid traits.Methods Nine hundred nine (909) T2DM patients were collected from Tianjin, north China. Clinical characteristics and biochemistry tests were documented for all subjects, genomic DNAs were extracted from peripheral whole blood samples using the high-salt method. Fifty-nine (59) SNPs in37candidate genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Association study were carried out by PLINK for hypertension, plasma glucose, lipids, and insulin resistance related phenotypes. Genotype interactions (epistasis) were also tested among SNPs in candidate genes and related phenotypes.Results1. Association analyse of discrete traits showed associations among ABI2gene SNPs (rs62183937, rs11675251, rs3731652and rsl376877) and the affection status of hypertension, P-values were1.823×10-4,0.008,0.009,and0.020, respectively.2. Associations were found among CDKAL1gene SNPs and body weight (BMI, rs10946398and rs7756992, P=0.007, and0.021, respectively). The same2SNPs also yielded P values of0.007and0.021for fasting plasma glucose (FPG)/fasting insulin (FINS) ratio. Multiple SNPs in MYH9gene were associated with GHbAlc (rs2269532, rs2071731, and rs739097, P-values were0.015,0.015, and0.023, respectively). The MYH9gene SNP rs739097was also associated with2-hour glucose (P2hG, P=0.006).3. Haplotype analyses were performed for ABI2and MYH9gene SNPs. The P-value was3.076x10-4between the rs62183937-rs11675251-rs3731652-rs1376877 "G-A-G-C" haplotype of ABI2gene and hypertension. Moreover, we found an association between the rs735853-rs875726-rs2009930"G-A-T" haplotype of MYH9gene and cerebrovascular disease (P=0.001). The rs735853-rs875726-rs2009930"G-G-C" haplotype of MYH9was also associated with total cholesterol (TC, P=0.006).4. Genotype interaction assays of dichotomic variables showed that the SNP rsl3266634of SLC30A8gene was interacted with rs2269532and rs2071731of MYH9gene for hypertension (P=9.087×10-4and9.087×10-4respectively). Genotype interactions were also observed among SF11gene SNPs (rs5749286and rs5753669) and rs7578326in IRS1for hypertension (P=2.588×10-4and1.959×10-4, respectively).5. Genotype interaction analyses of quantitative traits showed that the SNP rs62183937in ABI2gene was interacted with rs11067076and rs11067083in TBX5gene (P=1.220×10-7and8.920×10-6, respectively) for FPG. The SNP rs3731652in ABI2gene were also interacted with rs11067076and rs11067083in TBX5for FPG (P=1.150×10-6and1.10×10-5, respectively). Multiple genotype interactions were found among SNPs rs62183937, rs11675251and rs3731652in ABI2and rs2231142in ABCG2gene for QUICKI (P=1.350×10-5,3.730×10-5, and3.280×10-5, respectively). Moreover, we have observed interactions among the same3SNPs (rs62183937, rs11675251and rs3731652) in ABI2gene and rs1526167in TOX gene for QUICKI (P=5.529×10-4,9.785×10-4, and8.496×10-4, respectively).Conclusions In this study, we have genotyped59SNPs of37candidate genes in909T2DM patients. Significant associations and genotype interactions were found among ABI2, MYH9, CDKAL1, SLC30A8, and TBX5gene SNPs and T2DM related phenotypes. Especially, we are found intensive associations among the ABI2gene SNPs and hypertension, FPG, and other glucose-insulin resistance related phenotypes. Moreover, this study also suggested genotype interactions among ABI2and TBX5gene SNPs for FPG, as well as epistasis among MYH9and SLC30A8genes SNPs for hypertension. |
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