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早发型子痫前期女性白细胞介素10基因启动子多态性

Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia.

作者信息

Sowmya S, Sri Manjari K, Ramaiah A, Sunitha T, Nallari P, Jyothy A, Venkateshwari A

机构信息

Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, India.

出版信息

Clin Exp Immunol. 2014 Nov;178(2):334-41. doi: 10.1111/cei.12402.

Abstract

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (-1082 G/A; -592 A/C and -819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 -819 C allele (P = 0·003) and -592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to -1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: -1082A with -819C (P = 0·0016); -1082G with -819C (P = 0·0018); -819C with -592C (P = 0·001); -1082A with -592C (P = 0·032); and -1082G with -592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia.

摘要

子痫前期是人类妊娠最严重的病症之一,1型辅助性T细胞(Th1)/Th2失衡在其病因学中起主要作用。Th2细胞因子白细胞介素(IL)-10在维持妊娠中起重要作用。本研究旨在了解IL-10启动子多态性(-1082 G/A;-592 A/C和-819 C/T)及其单倍型在早发型子痫前期中的作用。本研究纳入了印度海得拉巴Petlaburz政府妇产医院的120例患者以及同等数量的正常妊娠女性。采用标准的扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)进行基因分型,随后进行琼脂糖凝胶电泳。应用适当的统计方法检验结果的显著性。结果发现,与对照组相比,患者中IL-10 -819 C等位基因(P = 0.003)和-592 A等位基因(P = 0.005)的频率显著增加。-1082启动子多态性方面未发现显著差异。对IL-10单核苷酸多态性(SNP)的单倍型分析显示,与ACC单倍型存在显著关联,患者的风险比对照组增加了两倍。两种常见的IL-10单倍型(GCC和ATA)的频率未显示任何显著差异。此外,双倍型分析揭示了五种与疾病相关的基因型:-1082A与-819C(P = 0.0016);-1082G与-819C(P = 0.0018);-819C与-592C(P = 0.001);-1082A与-592C(P = 0.032);以及-1082G与-592C(P = 0.005)。这些发现支持了IL-10基因多态性在早发型子痫前期发病机制中起作用的观点。

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