Wei Shudan, Yu Xiangyuan, Wen Xiaolan, Zhang Min, Lang Qi, Zhong Ping, Huang Bo
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Front Genet. 2022 Jun 6;13:830446. doi: 10.3389/fgene.2022.830446. eCollection 2022.
The involvement of oxidative stress in the pathological process of hypertensive disorders of pregnancy (HDP) gives rise to the interest in exploring the association of genetic variations in antioxidant metallothionein () genes with HDP susceptibility. Seventeen single-nucleotide polymorphisms(SNPs) in genes were selected to conduct genotyping based on a case-control study consisting of 371 HDP cases (pregnancy with chronic hypertension (66), gestational hypertension (172), and preeclampsia or preeclampsia superimposed on chronic hypertension (133)) and 479 controls. The association between SNPs in and the risk of HDP was estimated with unconditional logistic regression analysis and further tested with the false-positive report probability (FPRP) procedure. The joint effects of SNPs on the HDP risk were assessed by haplotype analysis. After the adjustment for age and pre-pregnancy body mass index (pre-BMI) in the logistic regress analysis and followed by the FPRP test, the genetic variation rs10636 (OR = 0.46, 95% CI: 0.30-0.71 for GG vs. CC, = 0.000 and OR = 0.48, 95% CI: 0.32-0.73 for GG vs. CG/CC, = 0.001) in was associated with gestational hypertension. Other four SNPs, that is, rs11076161 (OR = 1.89, 95% CI: 1.35-2.63 for GG vs. GA/AA, = 0.000) in ; rs7191779 (OR = 1.54, 95% CI: 1.11-2.13 for CC vs. CG/GG, = 0.010) in ; rs8044719 (OR = 0.57, 95% CI: 0.40-0.80 for GT vs. GG, = 0.001) in ; and rs8052334 (OR = 1.52, 95% CI: 1.10-2.11 for TT vs. TC/CC, = 0.012) in were significantly associated with the susceptibility of HDP. The haplotype analysis among 11, 10, 10, and seven SNPs in , , , , and genes showed that eight (A-C-G-T-C-G-A-G-C-G-C, OR = 4.559; A-C-T-C-C-C-A-G-C-G-C, OR = 5.777; A-C-T-T-C-G-A-G-C-G-C, OR = 4.590; G-A-T-C-C-G-C-G-G-C-C, OR = 4.065; G-A-T-C-G-C-C-G-G-C-C, OR = 4.652; G-A-T-T-C-C-C-G-G-C-C, OR = 0.404; G-C-T-C-C-C-A-G-G-C-C, OR = 1.901; G-C-T-T-C-C-A-G-G-C-C, and OR = 3.810), five (C-G-A-T-C-A-C-C-G-G, OR = 2.032; C-G-A-T-C-G-C-C-G-G, OR = 2.077; G-A-C-T-C-A-C-C-T-G, OR = 0.564; G-G-A-G-C-A-C-C-G-G, OR = 5.466; G-G-A-T-T-A-G-C-G-G, and OR = 0.284), five (A-C-G-T-C-G-A-G-C-C, OR = 2.399; A-C-T-C-C-C-C-T-G-G, OR = 0.259; G-A-T-C-C-C-C-G-G-C, OR = 1.572; G-A-T-C-G-C-C-G-G-C, OR = 0.001; G-C-T-C-G-C-A-G-G-C, and OR = 2.512), and five (A-C-T-C-C-C-G, OR = 0.634; G-A-G-C-C-C-G, OR = 4.047; G-A-T-T-G-C-G, OR = 0.499; G-C-G-T-C-A-G, and OR = 7.299; G-C-T-C-C-A-G, OR = 1.434) haplotypes were significantly associated with pregnancy with chronic hypertension, gestational hypertension, preeclampsia, or preeclampsia superimposed on chronic hypertension and HDP. These variant alleles and their combination patterns may be used as genetic markers for predicting HDP susceptibility.
氧化应激参与妊娠高血压疾病（HDP）的病理过程，这引发了人们对探索抗氧化金属硫蛋白（）基因的遗传变异与HDP易感性之间关联的兴趣。基于一项病例对照研究，选择了基因中的17个单核苷酸多态性（SNP）进行基因分型，该研究包括371例HDP病例（慢性高血压合并妊娠（66例）、妊娠期高血压（172例）以及子痫前期或子痫前期合并慢性高血压（133例））和479例对照。通过无条件逻辑回归分析估计基因中SNP与HDP风险之间的关联，并进一步用假阳性报告概率（FPRP）程序进行检验。通过单倍型分析评估SNP对HDP风险的联合效应。在逻辑回归分析中对年龄和孕前体重指数（孕前BMI）进行调整后，接着进行FPRP检验，基因中的遗传变异rs10636（GG与CC相比，OR = 0.46，95%CI：0.30 - 0.71， = 0.000；GG与CG/CC相比，OR = 0.48，95%CI：0.32 - 0.73， = 0.001）与妊娠期高血压相关。其他四个SNP，即基因中的rs11076161（GG与GA/AA相比，OR = 1.89，95%CI：1.35 - 2.63， = 0.000）；基因中的rs7191779（CC与CG/GG相比，OR = 1.54，95%CI：1.11 - 2.13， = 0.010）；基因中的rs8044719（GT与GG相比，OR = 0.57，95%CI：0.40 - 0.80， = 0.001）；以及基因中的rs8052334（TT与TC/CC相比，OR = 1.52，95%CI：1.10 - 2.11， = 0.012）与HDP的易感性显著相关。对基因、、、和中11个、10个、10个和7个SNP的单倍型分析表明，八个单倍型（A - C - G - T - C - G - A - G - C - G - C，OR = 4.559；A - C - T - C - C - C - A - G - C - G - C，OR = 5.777；A - C - T - T - C - G - A - G - C - G - C，OR = 4.590；G - A - T - C - C - G - C - G - G - C - C，OR = 4.065；G - A - T - C - G - C - C - G - G - C - C，OR = 4.652；G - A - T - T - C - C - C - G - G - C - C，OR = 0.404；G - C - T - C - C - C - A - G - G - C - C，OR = 1.901；G - C - T - T - C - C - A - G - G - C - C，OR = 3.810）、五个单倍型（C - G - A - T - C - A - C - C - G - G，OR = 2.032；C - G - A - T - C - G - C - C - G - G，OR = 2.077；G - A - C - T - C - A - C - C - T - G，OR = 0.564；G - G - A - G - C - A - C - C - G - G，OR = 5.466；G - G - A - T - T - A - G - C - G - G，OR = 0.284）、五个单倍型（A - C - G - T - C - G - A - G - C - C，OR = 2.399；A - C - T - C - C - C - C - T - G - G，OR = 0.259；G - A - T - C - C - C - C - G - G - C，OR = 1.572；G - A - T - C - G - C - C - G - G - C，OR = 0.001；G - C - T - C - G - C - A - G - G - C，OR = 2.512）以及五个单倍型（A - C - T - C - C - C - G，OR = 0.634；G - A - G - C - C - C - G，OR = 4.047；G - A - T - T - G - C - G，OR = 0.499；G - C - G - T - C - A - G，OR = 7.299；G - C - T - C - C - A - G，OR = 1.434）分别与慢性高血压合并妊娠、妊娠期高血压、子痫前期或子痫前期合并慢性高血压以及HDP显著相关。这些变异等位基因及其组合模式可作为预测HDP易感性的遗传标记。
