Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.
Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.
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母胎APOL1基因型和母国与子痫前期风险的联合关联
DOI：
10.1053/j.ajkd.2020.10.020
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Winkler CA
中科院分区：
文献类型：
--
作者：
Hong X;Rosenberg AZ;Zhang B;Binns-Roemer E;David V;Lv Y;Hjorten RC;Reidy KJ;Chen TK;Wang G;Ji Y;Simpson CL;Davis RL;Kopp JB;Wang X;Winkler CA
先兆子痫对黑人女性的影响尤为严重，是早产的主要原因，也是未来患高血压和慢性肾脏病（CKD）的风险因素。载脂蛋白L1（APOL1）肾脏风险等位基因在黑人中较为常见，是导致慢性肾脏病差异的重要原因。鉴于先兆子痫与慢性肾脏病之间的紧密联系，我们研究了母体和胎儿的APOL1风险等位基因是否会共同影响先兆子痫的风险，并探讨了APOL1与先兆子痫关联的潜在调节因素。
巢式病例对照研究。
来自波士顿出生队列的426对黑人母婴（275名非裔美国人；151名海地人）。
母体和胎儿的APOL1风险等位基因
先兆子痫
采用经人口统计学特征调整的逻辑回归模型，分析胎儿和母体的APOL1风险等位基因与先兆子痫风险之间的关联，并研究母体原籍国对效应的修饰作用。
胎儿的APOL1风险等位基因往往与先兆子痫风险增加有关，但在整个基因分型人群中无统计学意义。然而，这种关联受到母体原籍国的影响（交互检验P < 0.05）：在隐性（比值比=3.6，95%置信区间=1.3 - 9.7，P = 0.01）和加性（比值比=1.7，95%置信区间=1.1 - 2.6，P = 0.01）遗传模型下，胎儿的APOL1风险等位基因与非裔美国人先兆子痫风险增加显著相关，但在海地裔美国人中并非如此。此外，在APOL1位点上母体 - 胎儿基因型不一致与非裔美国人先兆子痫风险高2.6倍相关（P < 0.001）。
分层分析中的样本量有限；母体原籍国为自我报告；未收集母亲孕前估计的肾小球滤过率（eGFR）和蛋白尿数据；未测量的混杂社会和/或环境因素；无重复研究。
本研究支持以下假设：胎儿的APOL1肾脏风险等位基因在非裔美国人中以隐性遗传模式与先兆子痫风险增加相关，并表明母体 - 胎儿基因型不一致也与该风险相关。这些结论强调需要更好地理解母体 - 胎儿相互作用及其遗传和环境因素对先兆子痫种族差异的影响。
先兆子痫的特征是怀孕20周后血压升高以及其他异常（例如尿液中含蛋白质），对母亲及其婴儿都很危险。先前的研究发现，有非洲血统的个体可能携带增加慢性肾脏病风险的APOL1基因变异。本研究发现，胎儿的高危APOL1基因型以及母体 - 胎儿APOL1基因型不一致独立地导致非裔美国母亲患先兆子痫的风险增加。在海地母婴对中未观察到这种关联，可能是由于不同的环境暴露和文化环境所致。需要进一步的研究来理解为什么APOL1与先兆子痫的关联因母体原籍国不同而存在差异，并改善对有先兆子痫风险的母亲的管理。
Preeclampsia, disproportionately affecting Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Blacks, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers on the APOL1- preeclampsia association. Nested case-control study. 426 Black mother-infant pairs (275 African-Americans; 151 Haitians) from the Boston Birth Cohort. Maternal and fetal APOL1 risk alleles Preeclampsia Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia, and to investigate effect modification by maternal country-of-origin. Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country-of-origin (P < 0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African-Americans under recessive (OR=3.6, 95% CI=1.3–9.7, P=0.01) and additive (OR=1.7, 95% CI=1.1–2.6, P=0.01) genetic models, but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African-Americans. . Limited sample size in stratified analyses; self-reported maternal country-of-origin; Pre-pregnancy estimated blomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African-Americans, and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia. Preeclampsia, characterized by increased blood pressure after 20 weeks of pregnancy, as well as other abnormalities (e.g., protein in the urine), is dangerous to mothers and their infants. Previous studies found that individuals with African ancestry may carry APOL1 genetic variants that increase risk for chronic kidney disease. This study found that fetal high-risk APOL1 genotypes and maternal-fetal APOL1 genotype discordance independently contribute to preeclampsia risk in African-American mothers. This association was not observed in Haitian mother-infant pairs possibly because of different environmental exposures and cultural milieu. Additional studies are required to understand why APOL1 associations with preeclampsia differ by maternal country of origin and to improve management of mothers at risk for preeclampsia.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
分析方法检测出孕产妇/胎儿基因型不兼容，从而增加了先兆子痫的风险。
影响因子：
--
作者：
Parimi, Neeta;Tromp, Gerard;Kuivaniemi, Helena;Nien, Jyh Kae;Gomez, Ricardo;Romero, Roberto;Goddard, Katrina A. B.
通讯作者：
Goddard, Katrina A. B.
影响因子：
4
作者：
Hylenius, S;Andersen, AMN;Hviid, TVF
通讯作者：
Hviid, TVF
影响因子：
2.9
作者：
Bramham, Kate;Briley, Annette L.;Chappell, Lucy C.
通讯作者：
Chappell, Lucy C.
影响因子：
2.5
作者：
Bokslag, Anouk;van Weissenbruch, Mirjam;de Groot, Christianne J. M.
通讯作者：
de Groot, Christianne J. M.