Spracklen Cassandra N, Saftlas Audrey F, Triche Elizabeth W, Bjonnes Andrew, Keating Brendan, Saxena Richa, Breheny Patrick J, Dewan Andrew T, Robinson Jennifer G, Hoh Josephine, Ryckman Kelli K
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; Present address: Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA;
Am J Hypertens. 2015 Jul;28(7):915-23. doi: 10.1093/ajh/hpu242. Epub 2014 Dec 17.
Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia.
Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry.
The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04).
Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia.
大型流行病学研究支持血脂异常在先兆子痫中的作用；然而，先兆子痫的病因或血脂异常是否起因果作用仍不清楚。我们使用经过验证的血脂异常基因标记物，研究血脂异常的遗传易感性与先兆子痫风险之间的关联。
2002年8月至2005年5月期间，从爱荷华州初产妇的出生证明中选取先兆子痫病例（n = 164）和血压正常的对照（n = 110）。通过病历审查核实疾病状态。根据已确定的血脂位点，通过4个遗传风险评分（GRS）（总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯）评估血脂异常的遗传易感性。采用逻辑回归分析评估4种基因型评分与先兆子痫之间的关系。在一个独立的、具有欧洲血统的美国先兆子痫病例（n = 516）和对照（n = 1097）人群中进行重复分析。
与较高水平的TC、LDL-C和甘油三酯相关的GRS在爱荷华州人群或重复人群中均与先兆子痫风险无关联。与较低HDL-C相关的GRS与先兆子痫风险增加存在微弱关联（优势比（OR）= 1.03，95%置信区间（CI）= 0.99 - 1.07；P = 0.10）。在独立的重复人群中，与HDL-C GRS的关联也具有微弱显著性（OR = 1.03，95% CI：1.00 - 1.06；P = 0.04）。
我们的数据表明，HDL-C血脂异常水平的遗传易感性与先兆子痫风险增加之间可能存在关联，因此表明血脂异常可能是先兆子痫因果途径中的一个组成部分。
