背景:这项研究探讨了维生素D受体(VDR)中ApaI-TaqI单核苷酸多态性(SNP)与沙特女性妊娠期糖尿病(GDM)风险之间的关系,以及血清维生素D水平。方法:纳入90名GDM女性和90名非GDM女性,根据纳入单中心研究的孕妇的纳入和排除标准.使用乙二胺四乙酸(EDTA)管从180名孕妇中提取血液样品。血清样本用于测量维生素D,25-羟基维生素D(25(OH)D或骨化二醇),和脂质分布。血液用于测量血红蛋白A1c水平并分离DNA。对ApaI(rs79785232)进行聚合酶链反应(PCR),BsmI(rs1544410),FokI(rs2228570),和TaqI(rs731236)SNPs在VDR基因中使用限制性片段长度多态性分析。使用Sanger测序进行验证。使用各种统计软件包在有和没有GDM的患者之间进行统计分析。结果:Hardy-Weinberg平衡分析有统计学意义(p>0.05)。ApaI,Bsmi,TaqISNP与等位基因相关,基因型,和不同的遗传模型(p<0.05)。维生素D水平与缺乏水平相关(p=0.0002),以及正常和超重的体重指数(p=0.0004)。当用GDM协变量测量维生素D水平时,空腹血糖(FPG)(p=0.0001),餐后血糖(PPBG)(p<0.0001),口服葡萄糖耐量试验(OGTT)-1h(p=0.005),高密度脂蛋白(p=0.022),与低密度脂蛋白胆固醇(LDLc)(p=0.001)水平差异有统计学意义。当测量每个基因型的维生素D水平相似时,我们证实ApaISNP与足够的水平相关(p<0.0001),而BsmI,FokI,TaqI(p<0.05)与不足水平相关。逻辑回归模型证实,OGTT的第一个小时(p=0.005)与GDM密切相关,而方差分析证实,FPG和PPBG(p<0.05)与VDR基因中评估的所有SNP密切相关。此外,OGTT(p=0.048)和LDLc(p=0.049)的第二个小时与ApaI和FokISNP相关。此外,第一小时OGTT(p=0.045)和血脂参数(p<0.05)相关。单倍型分析显示所检查的SNP之间存在正相关,这似乎与多种SNP基因型的变异和组合增加女性GDM风险的假设相符.单倍型分析显示,不同的等位基因组合,例如AGCC,CATT,CGTC,AGTC,和CATT(p<0.05),强烈关联。连锁不平衡(LD)分析显示与所有组合的强关联(p<0.05)。在基因-基因相互作用中,所有可能的组合均呈正相关(p<0.05).结论:GDM女性患者维生素D水平低。ApaI,Bsmi,TaqISNP与基因型和等位基因频率相关(p<0.05)。维生素D与VDR基因中的SNPs相关,根据方差分析,逻辑回归,单倍型分析,LD分析,和广义多因子降维模型(p<0.05)。
Background: This study explored the association between ApaI-TaqI Single Nucleotide Polymorphisms (SNPs) in a Vitamin D receptor (VDR) and the risk of Gestational Diabetes Mellitus (GDM) in Saudi women, along with the serum levels of vitamin D. Methods: Ninety women with GDM and 90 non-GDM women were enrolled, based on the inclusion and exclusion criteria for pregnant women enrolled in a single-center study. Blood samples were retrieved from 180 pregnant women using ethylenediaminetetraacetic acid (EDTA) tubes. Serum samples were used to measure the vitamin D, 25-hydroxyvitamin D (25(OH)D or calcidiol), and lipid profiles. Blood was used to measure the hemoglobin A1c levels and to isolate the DNA. The polymerase chain reaction (PCR) was performed for the ApaI (rs79785232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236) SNPs in the VDR gene using restriction fragment length polymorphism analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed between the patients with and without GDM using various statistical software packages. Results: The Hardy-Weinberg equilibrium analysis was statistically significant (p > 0.05). The ApaI, BsmI, and TaqI SNPs were associated with alleles, genotypes, and different genetic models (p < 0.05). Vitamin D levels were associated with deficient levels (p = 0.0002), as well as with a normal and overweight body mass index (p = 0.0004). When vitamin D levels were measured with GDM covariates, the fasting plasma glucose (FPG) (p = 0.0001), postprandial blood glucose (PPBG) (p < 0.0001), oral glucose tolerance test (OGTT)-1 h (p = 0.005), high-density lipoprotein (p = 0.022), and low-density lipoprotein cholesterol (LDLc) (p = 0.001) levels were significantly different. When similar vitamin D levels were measured for each genotype, we confirmed that the ApaI SNP was associated with sufficient levels (p < 0.0001), whereas the BsmI, FokI, and TaqI (p < 0.05) were associated with insufficient levels. The logistic regression model confirmed that the first hour of the OGTT (p = 0.005) was strongly associated with GDM, whereas the analysis of variance confirmed that FPG and PPBG (p < 0.05) were strongly associated with all the SNPs evaluated in the VDR gene. Additionally, the second hour of the OGTT (p = 0.048) and LDLc (p = 0.049) were associated with the ApaI and FokI SNP. Moreover, the first hour OGTT (p = 0.045) and lipid profile parameters (p < 0.05) were associated. Haplotype analysis revealed positive associations among the examined SNPs, which seemed compatible with the hypothesis that variants and combinations of multiple SNP genotypes enhance the risk of GDM in women. Haplotype analysis revealed that different combinations of alleles, such as AGCC, CATT, CGTC, AGTC, and CATT (p < 0.05), were strongly associated. The linkage disequilibrium (LD) analysis showed a strong association with all combinations (p < 0.05). Among the gene-gene interactions, all possible combinations showed a positive association (p < 0.05). Conclusions: Low vitamin D levels were observed in women with GDM. The ApaI, BsmI, and TaqI SNPs were associated with genotype and allele frequencies (p < 0.05). Vitamin D and the SNPs in the VDR gene were associated, according to the ANOVA, logistic regression, haplotype analysis, LD analysis, and the generalized multifactor dimensionality reduction model (p < 0.05).