HIV 感染者特发性非肝硬化性门静脉高压的遗传决定因素。

Genetic determinants of idiopathic noncirrhotic portal hypertension in HIV-infected patients.

机构信息

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

出版信息

Clin Infect Dis. 2013 Apr;56(8):1117-22. doi: 10.1093/cid/cit001. Epub 2013 Jan 11.

DOI:10.1093/cid/cit001

PMID:23315321

Abstract

BACKGROUND

Noncirrhotic portal hypertension (NCPH) is a rare but potentially life-threatening complication in patients with human immunodeficiency virus (HIV). Cases of NCPH have been reported in HIV-negative individuals as result of treatment with thiopurines for leukemia or inflammatory bowel disease. Exposure to didanosine, which is also a purine analogue, predisposes to NCPH in the HIV setting. However, it is unclear why NCPH only develops in a small subset of didanosine-treated patients.

METHODS

A multicenter, case-control study was conducted to investigate the role of pharmacogenomics in NCPH in HIV patients with prior didanosine exposure. Three controls were chosen for each case, adjusted for sex, age, CD4 counts, plasma HIV-RNA, and site. Tagging 36 single-nucleotide polymorphisms (SNPs) at enzymes involved in the purine metabolism (inosine triphosphatase, 5'-nucleotidase cytosolic-II, purine nucleoside phosphorylase and xanthine oxidase) was performed using SNPlex microarray technology.

RESULTS

Eighty individuals were examined; 22 with NCPH and 58 matched controls. Two SNPs at the 5'-nucleotidase gene were associated with NCPH: rs11191561 (48% CG/GG vs 17% CC; P=.003) and rs11598702 (40% CC/CT vs 9% TT; P=.003). SNPs at another 2 loci at the xanthine oxidase gene were also associated with NCPH: rs1429376 (71% AA vs 23% CC/AC; P=.015) and rs1594160 (71% AA vs 23% CC/AC; P=.015). There was a cumulative risk of NCPH for these 4 SNPs: 7%, 26%, 42%, 50%, and 100%, respectively, for 0, 1, 2, 3, or all SNPs (P=.001).

CONCLUSIONS

SNPs at the 5'-nucleotidase and xanthine oxidase genes influence the risk of NCPH in HIV patients treated with didanosine.

摘要

背景

非肝硬化性门静脉高压症（NCPH）是人类免疫缺陷病毒（HIV）患者中一种罕见但潜在危及生命的并发症。在 HIV 阴性个体中，已有因白血病或炎症性肠病而接受硫嘌呤治疗而发生 NCPH 的病例报道。暴露于同样是嘌呤类似物的去羟肌苷会使 HIV 患者易患 NCPH。然而，为什么 NCPH 仅在一小部分接受去羟肌苷治疗的患者中发展，目前尚不清楚。

方法

进行了一项多中心病例对照研究，以调查先前接受过去羟肌苷治疗的 HIV 患者中，药物基因组学在 NCPH 中的作用。每个病例选择了 3 个对照，根据性别、年龄、CD4 计数、血浆 HIV-RNA 和部位进行了调整。使用 SNPlex 微阵列技术对涉及嘌呤代谢的酶（三磷酸肌苷酶、5'-核苷酸酶胞质 II、嘌呤核苷磷酸化酶和黄嘌呤氧化酶）中的 36 个单核苷酸多态性（SNP）进行了标记。

结果

共检查了 80 人，其中 22 人患有 NCPH，58 人作为匹配对照。核苷酸酶基因中的 2 个 SNP 与 NCPH 相关：rs11191561（48% CG/GG 比 17% CC；P=.003）和 rs11598702（40% CC/CT 比 9% TT；P=.003）。黄嘌呤氧化酶基因中的另外 2 个 SNP 也与 NCPH 相关：rs1429376（71% AA 比 23% CC/AC；P=.015）和 rs1594160（71% AA 比 23% CC/AC；P=.015）。这 4 个 SNP 的 NCPH 累积风险分别为：7%、26%、42%、50%和 100%，分别为 0、1、2、3 或所有 SNP（P=.001）。