NPFPC Contraceptives Adverse Reaction Monitoring Center, Jiangsu Institute of Planned Parenthood Research, 277 Feng Huang Xi Jie, Nanjing 210036, China.
Hum Genet. 2012 Aug;131(8):1337-44. doi: 10.1007/s00439-012-1161-7. Epub 2012 Apr 4.
Combined oral contraceptives (COC) use is a unique risk factor for stroke in women, and may modify the associations between genetic polymorphisms and stroke. To investigate whether the genetic variants identified in a recent genome-wide association study (GWAS) could be replicated in Chinese women, as well as, whether related risk was different in COC users, 451 stroke cases and 831 age- and region-matched controls were recruited from our cohort. Genotyping of 3 SNPs (rs700651, rs10958409, and rs1333040) was performed by the polymerase chain reaction assay with TaqMan probes. The history of contraceptive use and relevant information were obtained from a face-to-face interview. Odds ratios (OR) with 95 % confidence interval (CI) were estimated under conditional logistic regression model after adjustment for cardiovascular covariates. Our study replicated the associations of rs10958409 and rs1333040, with the risk of stroke, especially hemorrhagic subtype, but failed to confirm association of rs700651. COC use was associated with a 1.56-fold (OR 1.56, 95 % CI 1.21-2.01) increased risk of stroke. COC users with rs10958409 GA/AA or rs1333040 CT/TT genotypes had an increased risk of overall stroke by 1.59-fold (OR 2.59, 95 % CI 1.59-4.19) and 3.24-fold (OR 4.24, 95 % CI 1.71-10.49), respectively, compared with the non-users with wild-type genotypes. Moreover, the risk of hemorrhagic stroke increased by 4.81- and 15.06-fold when risk allele carriers of rs10958409 or rs1333040 who took COC. Our results confirmed the associations of two GWAS SNPs, also suggested combination effects of these genetic variants and COC use on stroke risk.
口服避孕药（COC）的使用是女性中风的一个独特危险因素，并且可能改变遗传多态性与中风之间的关联。为了研究最近全基因组关联研究（GWAS）中鉴定的遗传变异是否可以在中国女性中得到复制，以及 COC 使用者相关风险是否不同，从我们的队列中招募了 451 例中风病例和 831 例年龄和地区匹配的对照。通过聚合酶链反应试验和 TaqMan 探针对 3 个 SNP（rs700651、rs10958409 和 rs1333040）进行基因分型。通过面对面访谈获得避孕药使用史和相关信息。调整心血管协变量后，条件逻辑回归模型下估计比值比（OR）和 95%置信区间（CI）。我们的研究复制了 rs10958409 和 rs1333040 与中风风险的关联，尤其是出血性亚型，但未能证实 rs700651 的关联。COC 使用与中风风险增加 1.56 倍（OR 1.56，95%CI 1.21-2.01）相关。携带 rs10958409 GA/AA 或 rs1333040 CT/TT 基因型的 COC 使用者发生总体中风的风险增加 1.59 倍（OR 2.59，95%CI 1.59-4.19）和 3.24 倍（OR 4.24，95%CI 1.71-10.49），与携带野生型基因型的非使用者相比。此外，当携带 rs10958409 或 rs1333040 风险等位基因的 COC 使用者发生出血性中风时，风险增加 4.81-和 15.06 倍。我们的结果证实了两个 GWAS SNP 的关联，还提示了这些遗传变异与 COC 使用对中风风险的联合作用。
