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在南非一个非洲裔队列中,载脂蛋白L1基因内的母体变异与先兆子痫相关。

Maternal variants within the apolipoprotein L1 gene are associated with preeclampsia in a South African cohort of African ancestry.

作者信息

Thakoordeen-Reddy Semone, Winkler Cheryl, Moodley Jagidesa, David Victor, Binns-Roemer Elizabeth, Ramsuran Veron, Naicker Thajasvarie

机构信息

Womens' Health and HIV Research Group, Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, South Africa.

Basic Research Program, Frederick National Laboratory, Frederick, MD, United States.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2020 Mar;246:129-133. doi: 10.1016/j.ejogrb.2020.01.034. Epub 2020 Jan 27.

Abstract

OBJECTIVE

Preeclampsia (PE) is a complex pregnancy-specific medical disorder arising from an ischaemic placenta releasing factors causing widespread endothelial damage involving multiple organs systems, such as the renal system. Two variant alleles, termed G1 and G2, of the APOL1 gene are strongly associated with progressive renal disease and preeclampsia in the recessive or compound heterozygous state. Hence, we investigated the role of maternal APOL1 genotype in the pathogenesis of preeclampsia in South African women of African ancestry.

STUDY DESIGN

This case-control study comprised three groups of South African pregnant women of African ancestry attending a regional hospital in Durban, South Africa: mothers experiencing normotensive pregnancies, early onset preeclampsia and late onset preeclampsia underwent APOL1 genotyping. Differences in G1 and G2 allele and genotype frequencies were analysed for the three groups.

RESULTS

Our study revealed a significant association between the maternal APOL1 G1 risk allele and early-onset PE development (OR 2.2, p = 0.03). Among the EOPE group, 5 % [OR(95 %CI) 0.94 (0.29-3.12)] of the study population carried two risk alleles, 49 % [OR(95 %CI) 1.34 (0.77-2.3)] carried at least one risk allele, while 46 % of the participants did not carry either risk allele, compared to the normotensive pregnant group, where 52 % carried no risk allele, 42 % had at least one risk allele and 6 % of the women had both risk alleles.

CONCLUSION

Our results suggest that maternal APOL1 G1 risk allele may contribute to the development of early-onset PE in South African pregnant women of African ancestry either directly or by transmission of a APOL1 risk allele to the foetus.

摘要

目的

子痫前期(PE)是一种复杂的妊娠特异性医学疾病,由缺血性胎盘释放因子引起,导致包括肾脏系统在内的多个器官系统广泛的内皮损伤。载脂蛋白L1(APOL1)基因的两个变异等位基因,称为G1和G2,在隐性或复合杂合状态下与进行性肾病和子痫前期密切相关。因此,我们研究了非洲裔南非女性中母亲APOL1基因型在子痫前期发病机制中的作用。

研究设计

这项病例对照研究包括三组在南非德班一家地区医院就诊的非洲裔南非孕妇:血压正常的孕妇、早发型子痫前期孕妇和晚发型子痫前期孕妇,对她们进行了APOL1基因分型。分析了三组中G1和G2等位基因及基因型频率的差异。

结果

我们的研究揭示了母亲APOL1 G1风险等位基因与早发型子痫前期的发生之间存在显著关联(比值比2.2,p = 0.03)。在早发型子痫前期组中,5%[比值比(95%置信区间)0.94(0.29 - 3.12)]的研究人群携带两个风险等位基因,49%[比值比(95%置信区间)1.34(0.77 - 2.3)]携带至少一个风险等位基因,而46%的参与者未携带任何风险等位基因;相比之下,血压正常的孕妇组中,52%未携带风险等位基因,42%至少携带一个风险等位基因,6%的女性携带两个风险等位基因。

结论

我们的结果表明,母亲APOL1 G1风险等位基因可能直接或通过将APOL1风险等位基因传递给胎儿,导致非洲裔南非孕妇发生早发型子痫前期。

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