Genetic susceptibility analysis of GCLC rs17883901 polymorphism to preeclampsia in Chinese Han women

Abstract

Preeclampsia (PE) is a specific obstetric disorder that may result in maternal and neonatal morbidity and mortality. Increasing evidence has been indicated that some candidate genes related to oxidative stress, such as glutamate-cysteine ligase, catalytic subunit (GCLC), glutamate-cysteine ligase, modifier subunit (GCLM), involve in the pathogenesis of PE. After the genetic contribution of GCLC rs17883901 polymorphism was analyzed by TaqMan allelic discrimination real-time PCR in 1001 PE patients and 1182 normal pregnant women, a case-control association analysis was performed. Although no statistical difference was found in genetic distribution of rs17883901 in GCLC between PE and control group (χ² = 2.201, p = .333 by genotypic, χ² = 0.524, p = .469, OR = 0.932, 95%CI = 0.771–1.128 by allelic), significant differences in the genotypic frequencies were investigated between mild PE group (χ² = 6.999, p = .030) or late-onset PE group (χ² = 6.197, p = .045) and control group. Furthermore, when dividing the mild PE patients, the late-onset PE patients and the controls into TT/CT + CC, TT + CT/CC, and TT/CC subgroups, we found statistical differences between mild PE and controls (TT/CT + CC:χ² = 5.132, p = .023, OR = 2.948, 95%CI = 1.107–7.854; TT/CC:χ² = 4.564, p = .033, OR = 2.793, 95%CI = 1.046–7.460) as well as late-onset PE and controls (TT/CT + CC:χ² = 4.043, p = .044, OR = 2.248, 95%CI = 1.000–5.055). This is the first study to indicate GCLC rs17883901 polymorphism may be associated with a risk of mild PE and late-onset PE in Chinese Han women. However, additional well-designed studies with multi-ethnic and large-scale samples should be performed to validate our results.

摘要

子痫前期(PE)是产科的一种特有疾病, 可导致产妇和胎儿患病和死亡。越来越多的证据表明, 一些与氧化应激相关的候选基因, 如谷氨酸-半胱氨酸连接酶催化亚单位(GCLC)、谷氨酸-半胱氨酸连接酶修饰亚单位 (GCLM)等参与了PE的发病过程。采用TaqMan等位基因鉴别实时PCR技术对1001例PE患者和1182例正常孕妇GCLC rs17883901多态性的遗传贡献进行分析后, 进行病例—对照关联分析。虽然在PE和对照组间GCLC中rs17883901的基因分布未发现统计学差异(按基因型, χ²＝2.201, p＝0.333；按等位基因, χ²＝0.524, p＝0.469, OR＝0.932, 95%CI＝0.771-1.128), 但轻度PE组(χ²＝6.999, p＝0.030)或晚发型PE组(χ²＝6.197, p＝0.045)的基因型频率与对照组相比有统计学差异。在轻度PE组和晚发型PE组之间, rs17883901的基因型分布差异均无统计学意义(P>0.05)。此外, 将轻度PE患者、晚发型PE患者和对照组分为TT/CT＋CC、TT＋CT/CC和TT/CC亚组时, 我们发现轻度PE和对照组之间存在统计学差异(TT/CT＋CC：χ²＝5.132, p＝0.023, OR＝2.948, 95%CI＝1.107-7.854；TT/CC：χ²＝4.564, p＝0.033, OR＝2.793, 95%CI＝1.046-7.460), 晚发型PE和对照组也存在统计学差异(TT/CT＋CC：χ²＝4.564, p＝0.033, OR＝2.793, 95%CI＝1.046-7.460)。本研究首次表明GCLC rs17883901多态性可能与中国汉族女性轻度PE和晚发型PE的风险相关。然而, 还需要进行更多设计很好的多种族及大规模样本的研究来验证此结果。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Preeclampsia
• oxidative stress
• GCLC
• polymorphism

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Natural Science Fund Project of Shandong Province [ZR2019MH127].