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WNK1 和 AKR1C3 的新型 SNPs 与子痫前期有关。

Novel SNPs of WNK1 and AKR1C3 are associated with preeclampsia.

机构信息

Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing 100026, China.

Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing 100026, China.

出版信息

Gene. 2018 Aug 20;668:27-32. doi: 10.1016/j.gene.2018.05.055. Epub 2018 May 17.

Abstract

Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated. In this study, 13 SNPs of the five genes were genotyped in 276 preeclampsia patients and 229 age- and area-matched normal pregnancies in women of Chinese Northern Han origin. The 95% confidence interval (CI) and odds ratio (OR) were estimated by binary logistic regression. No obvious linkage disequilibrium or haplotypes were observed among these SNPs. Those with GG genotype and allele G of AKR1C3 (rs10508293) had a decreased risk of preeclampsia (adjusted OR = 3.011, 95% CI = 1.758-5.159, and adjusted OR = 1.745, 95% CI = 1.349-2.257, respectively). The AA genotype and allele A of WNK1 (rs1468326) were significantly associated with an increased risk in preeclampsia (adjusted OR = 2.307, 95% CI = 1.206-3.443, and adjusted OR = 1.663, 95% CI = 1.283-2.157, respectively). The findings indicate that the GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia and the AA genotype of WNK1 rs1468326 are related with an increased risk for preeclampsia.

摘要

子痫前期是一种妊娠高血压疾病,是围产期不良结局的最常见原因之一。子痫前期会增加未来发生高血压的风险。WNK1(赖氨酸缺陷蛋白激酶 1)、ADRB2(β2 肾上腺素能受体)、NEDD4L(泛素蛋白连接酶 NEDD4 样)、KLK1(激肽释放酶 1)的变体与高血压有关,而 AKR1C3(醛酮还原酶家族 1 成员 C3)与子痫前期有关。本研究调查了这 5 个候选子痫前期易感性基因中的单核苷酸多态性(SNP)与中国北方汉族人群相关特征的关联。在这项研究中,对 276 例子痫前期患者和 229 例年龄和地区匹配的正常妊娠妇女的 5 个基因的 13 个 SNP 进行了基因分型。采用二项逻辑回归估计 95%置信区间(CI)和比值比(OR)。这些 SNP 之间没有明显的连锁不平衡或单倍型。AKR1C3(rs10508293)的 GG 基因型和 G 等位基因的个体发生子痫前期的风险降低(校正 OR=3.011,95%CI=1.758-5.159,校正 OR=1.745,95%CI=1.349-2.257)。WNK1(rs1468326)的 AA 基因型和 A 等位基因与子痫前期的风险增加显著相关(校正 OR=2.307,95%CI=1.206-3.443,校正 OR=1.663,95%CI=1.283-2.157)。这些发现表明,AKR1C3 rs10508293 的 GG 基因型与子痫前期的低风险相关,而 WNK1 rs1468326 的 AA 基因型与子痫前期的高风险相关。

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