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位于2号染色体14区抑制素βB基因附近的单核苷酸多态性与中国汉族女性的子痫前期有关。

Single nucleotide polymorphisms near the inhibin beta B gene on 2q14 are associated with pre-eclampsia in Han Chinese women.

作者信息

Wang Q, Wang G, Guo C, Cao X, An L, Du M, Qiu Y, Yang Y, Wang Y, Wang S, Wang X, Ma X

机构信息

National Research Institute for Family Planning, Beijing, China.

Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2015 Oct;193:127-31. doi: 10.1016/j.ejogrb.2015.04.001. Epub 2015 Apr 15.

Abstract

CONTEXT AND OBJECTIVE

Pre-eclampsia (PE) is the most common medical complication of pregnancy encountered worldwide. A previous genome-wide association study showed that three single nucleotide polymorphisms (SNPs) located near the inhibin beta B gene (INHBB) - rs12711941 (T>G), rs7576192 (A>G) and rs7579169 (T>C) - were associated with PE in Australian women. The present study was undertaken to assess the genetic association between these three SNPs and the risk of PE in Han Chinese women.

PATIENTS

One hundred and eighty-one pregnant women with PE and 203 healthy pregnant women (controls) were recruited from the Department of Obstetrics and Gynaecology at the Shengjing Hospital of China Medical University from October 2012 to June 2013.

STUDY DESIGN

PE patients and controls underwent clinical and biochemical examination. The three SNPs were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PE patients were divided into various subgroups for comparison with controls.

RESULTS

The rs7579169 CC genotype was found to have a significantly higher frequency in PE patients than in controls [TT vs TC+CC: odds ratio (OR)=2.278, p=0.040], indicating that the C allele of rs7579169 confers a risk for PE [OR=1.4440, 95% confidence interval (CI) 1.0517-1.9827, p=0.0229]. The rs7576192 genotype showed significant differences between controls and multiparous PE patients (χ(2)=4.6088, df=1, P=0.0319, OR=0.6379, 95% CI 0.4223-0.9634). However, neither allele nor genotype frequencies of rs12711941 differed significantly between patients and controls in any genetic models or subgroup analyses. Haplotype analysis revealed that the H1 haplotype (G-G-C) was associated with PE (OR=1.437, 95% CI 1.034-1.997, p<0.05), whereas the H2 haplotype (G-G-T) offered protection against PE (OR=0.482, 95% CI 0.232-1.001, p<0.05).

CONCLUSION

Pregnant Han Chinese women carrying the rs7579169 CC genotype and G-G-C haplotype are significantly more likely to develop PE, especially late-onset and multiparous cases.

摘要

背景与目的

子痫前期(PE)是全球范围内妊娠最常见的医学并发症。先前的全基因组关联研究表明,位于抑制素βB基因(INHBB)附近的3个单核苷酸多态性(SNP)——rs12711941(T>G)、rs7576192(A>G)和rs7579169(T>C)——与澳大利亚女性的PE相关。本研究旨在评估这3个SNP与中国汉族女性PE风险之间的遗传关联。

患者

2012年10月至2013年6月,从中国医科大学附属盛京医院妇产科招募了181例PE孕妇和203例健康孕妇(对照组)。

研究设计

对PE患者和对照组进行临床和生化检查。采用基质辅助激光解吸/电离飞行时间质谱法对这3个SNP进行基因分型。将PE患者分为不同亚组与对照组进行比较。

结果

发现rs7579169的CC基因型在PE患者中的频率显著高于对照组[TT与TC+CC比较:优势比(OR)=2.278,p=0.040],表明rs7579169的C等位基因赋予PE风险[OR=1.4440, 95%置信区间(CI)1.0517-1.9827,p=0.0229]。rs7576192基因型在对照组与经产妇PE患者之间存在显著差异(χ(2)=4.6088,自由度=1,P=0.0319,OR=0.6379,95%CI 0.4223-0.9634)。然而,在任何遗传模型或亚组分析中,rs12711941的等位基因频率和基因型频率在患者与对照组之间均无显著差异。单倍型分析显示,H1单倍型(G-G-C)与PE相关(OR=1.437,95%CI 1.034-1.997,p<0.05),而H2单倍型(G-G-T)对PE有保护作用(OR=0.482,95%CI 0.232-1.001,p<0.05)。

结论

携带rs7分79169 CC基因型和G-G-C单倍型的中国汉族孕妇发生PE的可能性显著更高,尤其是晚发型和经产妇。

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