ABSTRACT
We explored the associations of INSR and mTOR, 2 key genes in the insulin signaling pathway, and the susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817, rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in 89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes patients with diabetic nephropathy, and 120 healthy control subjects. Statistical analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination analyses between rs2059806 and rs7212142 were also performed using the X(2) test and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818, and rs9674559) showed no association with type 2 diabetes mellitus or diabetic nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142 polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010, OR = 0.501, 95%CI = 0.288- 0.871), but showed no relationship with type 2 diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had a combined effect on susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Our results suggest that both INSR and mTOR play a role in the predisposition of the Han Chinese population to type 2 diabetic nephropathy, but the genetic predisposition may show some differences.
Subject(s)
Antigens, CD/genetics , Asian People/genetics , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Polymorphism, Single Nucleotide , Receptor, Insulin/genetics , TOR Serine-Threonine Kinases/genetics , Adult , Aged , Case-Control Studies , China , Female , Genetic Predisposition to Disease , Genotype , Genotyping Techniques , Humans , Male , Middle Aged , Sequence Analysis, DNAABSTRACT
Patterns of DNA methylation are established and maintained by a family of DNA methyltransferases (DNMTs). Aberrant promoter DNA methylation of tumor suppressor genes is found in breast cancer. Association studies between DNMT gene polymorphisms and breast cancer in various populations have reported inconsistent results. This study assessed the associations of single nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2 with breast cancer among Han Chinese women from South China. Sixteen SNPs (rs2114724, rs2228611, rs2228612, rs8101866, and rs16999593 in DNMT1; rs13420827, rs11887120, rs13428812, rs1550117, rs11695471, and rs6733301 in DNMT3A; rs2424908, rs2424913, and rs6087990 in DNMT3B; rs113593938 in DNMT3L, and rs11254413 in DNMT2) in 408 women with breast cancer and 469 controls were genotyped using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Two SNPs, rs16999593 in DNMT1 and rs2424908 in DNMT3B, were significantly associated with breast cancer risk. The heterozygous genotype CT of rs16999593 was associated with increased breast cancer risk [odds ratio (OR) = 1.60; 95% confidence interval (95%CI) = 1.20-2.14; P = 0.0052], whereas rs2424908 was associated with decreased risk (OR = 0.62; 95%CI = 0.46-0.84; P = 0.0061). Other DNMT polymorphisms showed no significant associations with breast cancer risk in the study population. Haplotype CGTC of rs2114724, rs2228611, rs8101866, and rs16999593 in DNMT1 differed significantly as a risk factor between the case and control groups (OR = 1.51; 95%CI = 1.18-1.93; P = 0.0012). The heterozygous genotypes of rs16999593 in DNMT1 and rs2424908 in DNMT3B were strongly associated with breast cancer risk.