脂肪量与肥胖相关基因变异与HIV感染患者的脂肪肝疾病有关。

Fat mass and obesity-associated gene variations are related to fatty liver disease in HIV-infected patients.

作者信息

Núñez-Torres R, Macías J, Rivero-Juarez A, Neukam K, Merino D, Téllez F, Merchante N, Gómez-Mateos J, Rivero A, Pineda J A, Real L M

机构信息

Unit of Infectious Diseases and Microbiology, Valme University Hospital, Seville, Spain.

Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.

出版信息

HIV Med. 2017 Sep;18(8):546-554. doi: 10.1111/hiv.12489. Epub 2017 Jan 24.

DOI:10.1111/hiv.12489

PMID:28116842

Abstract

OBJECTIVES

Fatty liver disease (FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV-infected patients.

METHODS

FLD was defined as a value of the controlled attenuation parameter (CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population.

RESULTS

Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [P = 0.009; adjusted odds ratio 1.88; 95% confidence interval (CI) 1.17-3.01].

CONCLUSIONS

Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors.

摘要

目的

脂肪性肝病（FLD）在HIV感染患者中很常见。肥胖和2型糖尿病（T2DM）与FLD密切相关。由于脂肪量与肥胖相关（FTO）基因内的遗传变异与这两种疾病都有关联，我们的目的是评估FTO内先前与肥胖或T2DM相关的单核苷酸多态性（SNP）与HIV感染患者FLD的关联。

方法

FLD定义为通过瞬时弹性成像获得的控制衰减参数（CAP）≥238 dB/m的值。使用定制的金门协议对421名个体的FTO内含子1中的四个SNP（rs11642841、rs8050136、rs9939609和rs9940128）进行基因分型。结果在由另外206名HIV感染患者组成的验证样本中得到重复。在整个人口中进行多变量逻辑回归分析。

结果

三个SNP（rs8050136、rs9939609和rs9940128）与FLD相关，其中rs9940128显示出最强的关联。这种多态性在验证样本中也与FLD相关。总共对627名HIV感染患者进行了rs9940128基因分型，其中包括267名（42.6%）被诊断为FLD的个体。rs9940128 AA携带者中FLD的发生率为55.7%（113名个体中的63名），而没有这种基因型的患者中FLD的发生率为39.7%（514名个体中的204名）[P = 0.009；调整后的优势比1.88；95%置信区间（CI）1.17 - 3.01]。