Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
BJOG. 2021 Jan;128(1):55-65. doi: 10.1111/1471-0528.16441. Epub 2020 Sep 14.
To assess whether women with a genetic predisposition to medical conditions known to increase pre-eclampsia risk have an increased risk of pre-eclampsia in pregnancy.
Case-control study.
Pre-eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene-centric array.
Significant single-nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre-eclampsia. Odds of pre-eclampsia were compared across quartiles of the genetic instrument and evaluated for significance.
Genetic predisposition to medical conditions and relationship with pre-eclampsia.
An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre-eclampsia (DBP, overall OR 1.11, 95% CI 1.01-1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00-1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82-0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early-onset pre-eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08-1.56, P = 0.005). For other traits, there was no evidence of an association.
These results suggest that the underlying genetic architecture of pre-eclampsia may be shared with other disorders, specifically hypertension and obesity.
A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre-eclampsia.
评估具有已知增加子痫前期风险的医学病症遗传倾向的女性在妊娠期间是否患子痫前期的风险增加。
病例对照研究。
在来自五个美国地点的具有欧洲血统的女性中，子痫前期病例（n=498）和对照（n=1864）进行了心血管基因芯片的基因分型。
利用具有已发表全基因组关联研究（GWAS）的七个疾病类别（心血管、炎症/自身免疫、胰岛素抵抗、肝脏、肥胖、肾脏和血栓形成倾向）中 21 个特征的显著单核苷酸多态性（SNP），为每个特征创建一个遗传工具。多变量逻辑回归用于检验每个连续比例遗传工具与子痫前期的关联。比较遗传工具四分位数之间子痫前期的几率，并评估其显著性。
对医疗条件的遗传倾向与子痫前期的关系。
舒张期血压（DBP）升高和体重指数（BMI）升高的风险等位基因负担增加与子痫前期风险增加相关（DBP，总体 OR 1.11，95%CI 1.01-1.21，P=0.025；BMI，OR 1.10，95%CI 1.00-1.20，P=0.042），而与碱性磷酸酶（ALP）升高相关的等位基因具有保护作用（OR 0.89，95%CI 0.82-0.97，P=0.008），这主要是由于 FADS 基因区域变异的多效性所致。DBP 遗传基因座的影响在早发型子痫前期病例中更大（<34 孕周，OR 1.30，95%CI 1.08-1.56，P=0.005）。对于其他特征，没有证据表明存在关联。
这些结果表明，子痫前期的潜在遗传结构可能与其他疾病，特别是高血压和肥胖有关。
对舒张压升高和肥胖的遗传易感性增加了子痫前期的风险。
