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内皮型一氧化氮合酶单倍型与玛雅混血女性先兆子痫有关。

Endothelial nitric oxide synthase haplotypes are associated with preeclampsia in Maya mestizo women.

机构信息

División de Investigación Biomédica, Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México.

出版信息

Dis Markers. 2011;31(2):83-9. doi: 10.3233/DMA-2011-0804.

Abstract

Preeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms in eNOS or their haplotypes are associated with preeclampsia in Maya mestizo women. A case-control study was performed where 127 preeclamptic patients and 263 controls were included. Genotyped and haplotypes for the -768T→C, intron 4 variants, Glu298Asp of eNOS were determined by PCR and real-time PCR allelic discrimination. Logistic regression analysis with adjustment for age and body mass index (BMI) was used to test for associations between genotype and preeclampsia under recessive, codominant and dominant models. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r^{2}, and haplotype analysis was conducted. Women homozygous for the Asp298 allele showed an association of preeclampsia. In addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298 haplotype was significantly more frequent in preeclamptic patients than in controls (0.143 vs. 0.041, respectively; OR =3.01; 95% CI = 1.74-5.23; P =2.9 × 10^{-4}).Despite the Asp298 genotype in a recessive model associated with the presence of preeclampsia in Maya mestizo women, we believe that in this population the -786C-4b-Asp298 haplotype is a better genetic marker.

摘要

子痫前期是一种特定的妊娠疾病,被认为具有遗传成分。本研究旨在探讨内皮型一氧化氮合酶(eNOS)中的三个多态性或其单倍型是否与玛雅混血女性的子痫前期有关。进行了病例对照研究,其中包括 127 例子痫前期患者和 263 例对照。通过 PCR 和实时 PCR 等位基因鉴别,确定了 -768T→C、内含子 4 变异、eNOS 的 Glu298Asp 的基因型和单倍型。使用逻辑回归分析,在调整年龄和体重指数(BMI)后,在隐性、共显性和显性模型下,测试基因型与子痫前期之间的关联。通过直接相关< formula>r^{2}计算单核苷酸多态性之间的成对连锁不平衡,并进行单倍型分析。Asp298 等位基因纯合的女性子痫前期发病风险增加。此外,单倍型频率分析显示,-786C-4b-Asp298 单倍型在子痫前期患者中明显比对照组更常见(分别为 0.143 和 0.041;OR =3.01;95% CI = 1.74-5.23;P =2.9 × 10^{-4})。尽管在玛雅混血女性中,eNOS 基因的 Asp298 基因型在隐性模型中与子痫前期的存在相关,但我们认为在该人群中,-786C-4b-Asp298 单倍型是更好的遗传标志物。

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