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Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease.

Abstract：

BACKGROUND & AIMS:Hepatopulmonary syndrome (HPS) affects 10%-30% of patients with cirrhosis and portal hypertension and significantly increases mortality. Studies in experimental models indicate that pulmonary angiogenesis contributes to the development of HPS, but pathogenesis in humans is poorly understood. We investigated genetic risk factors for HPS in patients with advanced liver disease. METHODS:We performed a multicenter case-control study of patients with cirrhosis being evaluated for liver transplantation. Cases had an alveolar-arterial oxygen gradient > or = 15 mm Hg (or > or =20 mm Hg if age > 64 years) and contrast echocardiography with late appearance of microbubbles after venous injection of agitated saline (intrapulmonary vasodilatation); controls did not meet both criteria for case status. The study sample included 59 cases and 126 controls. We genotyped 1086 common single nucleotide polymorphisms (SNPs) in 94 candidate genes. RESULTS:Forty-two SNPs in 21 genes were significantly associated with HPS after adjustments for race and smoking. Eight genes had at least 2 SNPs associated with disease: CAV3, ENG, NOX4, ESR2, VWF, RUNX1, COL18A1, and TIE1. For example, rs237872 in CAV3 showed an odds ratio of 2.75 (95% confidence interval: 1.65-4.60, P = .0001) and rs4837192 in ENG showed an odds ratio of 0.35 (95% confidence interval: 0.14-0.89, P = .027). Furthermore, variation in CAV3 and RUNX1 was associated with HPS in gene-based analyses. CONCLUSIONS:Polymorphisms in genes involved in the regulation of angiogenesis are associated with the risk of HPS. Further investigation of these biologic pathways might elucidate the mechanisms that mediate the development of HPS in certain patients with severe liver disease.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Roberts KE,Kawut SM,Krowka MJ,Brown RS Jr,Trotter JF,Shah V,Peter I,Tighiouart H,Mitra N,Handorf E,Knowles JA,Zacks S,Fallon MB,Pulmonary Vascular Complications of Liver Disease Study Group.

doi

10.1053/j.gastro.2010.03.044

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

130-9.e24

issue

1

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(10)00463-4

journal_volume

139

pub_type

杂志文章,多中心研究

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