Science Department, Turtle Mountain Community College, Belcourt, North Dakota, United States of America.
PLoS One. 2013 Aug 5;8(8):e71231. doi: 10.1371/journal.pone.0071231. Print 2013.
The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease.
This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped.
A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97-2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00-6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16-3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16-1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants.
The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE.
子痫前期（PE）的病因尚不清楚；但人们普遍认为正常妊娠对母体免疫系统是一个特殊的挑战。C 反应蛋白是先天免疫系统的重要组成部分；我们之前曾报道过 PE 与 CRP 多态性 rs1205 之间存在关联。我们的目的是探讨其他 CRP 变体的影响。IBC（Cardiochip）基因分型微阵列侧重于与心血管疾病病理生理学相关的候选基因和途径。
本研究招募了来自美国印第安人社区的 140 例 PE 病例和 270 例匹配对照，其中 95 例符合重度 PE 标准。分析了 10 个合适的 CRP 单核苷酸多态性（SNP）的 IBC 阵列基因型。还对 178 例病例和 427 例欧洲血统对照进行了复制样本的基因分型。
rs3093068 配对比对的分布存在显著差异（p 值<0.05）；rs876538、rs2794521 和 rs3091244 的 Bonferroni 校正差异（P<0.005）。rs3093068 和 rs876538 模型的单变量条件逻辑回归比值比（OR）具有统计学意义。调整母亲年龄、初产和 BMI 的多变量逻辑模型减弱了 rs876538（OR 1.58，P=0.066，95%CI 0.97-2.58）和 rs3093068（OR 2.59，P=0.050，95%CI 1.00-6.68）的效应。上述两种风险基因型的加性风险评分显示多变量调整后的 OR 为 2.04（P=0.013，95%CI 1.16-3.56）。复制样本还显示 PE 与 rs876538 等位基因之间存在显著关联（OR=1.55，P=0.01，95%CI 2.16-1.10）。我们还展示了 CRP 变体 rs876538 和 rs3093068 的潜在功能。
先前与其他心血管疾病表型相关的 CRP 变体 rs876538 和 rs3093068 与该美国印第安人群中的 PE 具有提示性关联，进一步支持 CRP 在 PE 中的可能作用。
