Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals.
OBJECTIVE
Fatty liver disease (FLD) is frequently observed in HIV-infected patients and a cause of advanced liver disease. Genetic factors could play a role in determining risk for FLD development in those patients. The aim of this study was to evaluate the association of those single nucleotide polymorphisms (SNPs) previously found to be related to nonalcoholic FLD by genome-wide association analyses in the general population with the presence of FLD, including steatohepatitis, in HIV-infected individuals.


METHODS
This is a transversal study.


METHODS
A total of 431 HIV-infected patients were included in this study. All of them underwent a transient elastography with the controlled attenuation parameter examination and were genotyped for 19 selected SNPs. A controlled attenuation parameter value higher than 238 dB/m was selected to define the presence of FLD. Elevated alanine aminotransferase levels and presence of FLD was considered as a surrogate marker of steatohepatitis.


RESULTS
A total of 179 (41.5%) individuals showed FLD, including 122 (28.3%) with steatohepatitis. The rs12743824 and rs738491 SNPs were independently associated with FLD and steatohepatitis, respectively. For rs12743824, among 252 individuals without FLD, 182 (72.2%) were A-allele carriers vs. 111 (62%) of 179 patients with this disease (multivariate P = 0.006; adjusted odds ratio = 0.51; 95% confidence interval = 0.33-0.83). For rs738491, 20 (16.4%) of 122 patients with steatohepatitis were TT carriers vs. 18 (5.8%) of 309 patients without this condition (multivariate P = 0.005; adjusted odds ratio = 2.94; 95% confidence interval = 1.39-6.20).


CONCLUSIONS
LPPR4 and SAMM50 allelic variants are independent risk factors for FLD and steatohepatitis development, respectively, in HIV-infected individuals.
aUnidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme bInstituto de Biomedicina de Sevilla (IBIS), Seville cUnidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía dInstituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), Cordoba eUnidad de Enfermedades Infeccciosas, Hospital de la Línea de la Concepción, Cadiz fUnidad de Enfermedades Infecciosas, Complejo Hospitalario Universitario de Huelva, Huelva, Spain.
Juan
J
Macias
Antonio
A
Rivero-Juarez
Karin
K
Neukam
Francisco
F
Tellez
Dolores
D
Merino
Mario
M
Frias
Nicolás
N
Merchante
Antonio
A
Rivero
Juan A
JA
Pineda
Luis M
LM
Real
D000328:Adult; D003955:Diagnostic Tests, Routine; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D010711:Phosphatidate Phosphatase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
C579437:PLPPR4 protein, human; D010711:Phosphatidate Phosphatase