Luo L, Li D H, Wei S G, Zhang H B, Li S B, Zhao J
Department of Forensic Science, School of Medicine, Xi'an Jiaotong University/Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shaanxi, China.
Genet Mol Res. 2013 Sep 23;12(3):3879-86. doi: 10.4238/2013.September.23.6.
Endothelial nitric oxide synthase (eNOS) is an enzyme that influences placental human chorionic gonadotropin production during gestation. Previous studies have indicated an association between eNOS activity, implantation, and maintenance of pregnancy, but proposed associations between polymorphisms of the eNOS gene and recurrent miscarriage (RM) are controversial. To identify markers contributing to the genetic susceptibility to RM, we examined the potential association between RM and 8 single nucleotide polymorphisms (SNPs; rs1799983, rs2070744, rs11771443, rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the eNOS gene using the MassARRAY system (Sequenom, USA). The enrolled participants included 192 RM patients and 201 women with normal fertility as controls. The results showed that rs1799983 at exon 7 of the eNOS gene was significantly associated with RM (genotype: chi-square = 15.071, P = 0.001; allele: chi-square = 6.250, P = 0.016). Another significant association was observed for rs11771443 in the promoter (genotype: chi-square = 6.259, P = 0.044; allele: chi-square = 7.076, P = 0.008). Furthermore, strong linkage disequilibrium was observed in 3 blocks (D' > 0.9), and significantly fewer T-T-G haplotypes (chi-square = 5.981, P = 0.015) residing in block 1 were found in RM patients. These findings point to a role for eNOS gene polymorphisms in RM in the Chinese Han population and may be informative for future genetic or neurobiological studies of RM.
内皮型一氧化氮合酶（eNOS）是一种在妊娠期间影响胎盘人绒毛膜促性腺激素产生的酶。先前的研究表明eNOS活性、着床及维持妊娠之间存在关联，但eNOS基因多态性与复发性流产（RM）之间的拟议关联存在争议。为了确定导致RM遗传易感性的标志物，我们使用MassARRAY系统（美国Sequenom公司）检测了RM与eNOS基因上8个单核苷酸多态性（SNP；rs1799983、rs2070744、rs11771443、rs3918188、rs2853796、rs7830、rs1541861和rs2853792）之间的潜在关联。纳入的参与者包括192例RM患者和201例生育能力正常的女性作为对照。结果显示，eNOS基因第7外显子的rs1799983与RM显著相关（基因型：卡方 = 15.071，P = 0.001；等位基因：卡方 = 6.250，P = 0.016）。在启动子区域的rs11771443也观察到另一个显著关联（基因型：卡方 = 6.259，P = 0.044；等位基因：卡方 = 7.076，P = 0.008）。此外，在3个区域观察到强连锁不平衡（D' > 0.9）且在RM患者中位于区域1的T-T-G单倍型显著减少（卡方 = 5.981，P = 0.015）。这些发现表明eNOS基因多态性在中国汉族人群的RM中起作用，可能为未来RM的遗传或神经生物学研究提供信息。
