Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Environ Res. 2022 Sep;212(Pt A):113186. doi: 10.1016/j.envres.2022.113186. Epub 2022 Mar 28.
Carriage of high-risk APOL1 genetic variants is associated with increased risks for kidney diseases in people of African descent. Less is known about the variants' associations with blood pressure or potential moderators.
We investigated these associations in a pregnancy cohort of 556 women and 493 children identified as African American. Participants with two APOL1 risk alleles were defined as having the high-risk genotype. Blood pressure in both populations was measured at the child's 4-6 years visit. We fit multivariate linear and Poisson regressions and further adjusted for population stratification to estimate the APOL1-blood pressure associations. We also examined the associations modified by air pollution exposures (particulate matter ≤2.5 μ m in aerodynamic diameter [PM] and nitrogen dioxide) and explored other moderators such as health conditions and behaviors.
Neither APOL1 risk alleles nor risk genotypes had a main effect on blood pressure in mothers or children. However, each 2-μg/m increase of four-year average PM was associated with a 16.3 (95%CI: 5.7, 26.9) mmHg higher diastolic blood pressure in mothers with the APOL1 high-risk genotype, while the estimated effect was much smaller in mothers with the low-risk genotype (i.e., 2.9 [95%CI: -3.1, 8.8] mmHg; P = 0.01). Additionally, the associations of APOL1 risk alleles and the high-risk genotype with high blood pressure (i.e., SBP and/or DBP ≥ 90 percentile) were stronger in girls vs. boys (P = 0.02 and 0.005, respectively).
This study sheds light on the distribution of high blood pressure by APOL1 genetic variants and informs regulatory policy to protect vulnerable population subgroups.
携带高风险 APOL1 基因突变与非洲裔人群的肾脏疾病风险增加有关。然而,人们对这些变体与血压的关联以及潜在的调节因素知之甚少。
我们在一个由 556 名女性和 493 名被确定为非裔美国人的儿童组成的妊娠队列中研究了这些关联。具有两个 APOL1 风险等位基因的参与者被定义为具有高风险基因型。在儿童 4-6 岁就诊时测量了两个群体的血压。我们拟合了多元线性和泊松回归,并进一步调整了人群分层,以估计 APOL1-血压关联。我们还检查了空气污染暴露(空气动力学直径≤2.5μm 的颗粒物 [PM] 和二氧化氮)修饰的关联,并探索了其他调节因素,如健康状况和行为。
APOL1 风险等位基因或风险基因型都没有对母亲或儿童的血压产生主要影响。然而,在具有 APOL1 高风险基因型的母亲中,四年平均 PM 每增加 2μg/m,舒张压升高 16.3(95%CI:5.7,26.9)mmHg,而在具有低风险基因型的母亲中,估计的影响要小得多(即 2.9 [95%CI:-3.1,8.8]mmHg;P=0.01)。此外,APOL1 风险等位基因和高风险基因型与高血压(即 SBP 和/或 DBP≥90 百分位数)的关联在女孩中比男孩更强(分别为 P=0.02 和 0.005)。
这项研究揭示了 APOL1 遗传变异与高血压之间的分布关系,并为保护脆弱人群亚组的监管政策提供了信息。