Association of PNPLA3, TM6SF2 and HSD17B13 variants with NAFLD risk in HIV and non-HIV individuals
Keywords:
NAFLD, HIV, HSD17B13, PNPLA3, TM6SF2Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) has multiple risk factors, including genetic risk factors. Patients with certain genetic variants are more susceptible to the disease. People living with human immunodeficiency virus (PLWH) have higher prevalence of NAFLD compared to those without human immunodeficiency virus (HIV) infection. However, the evidence on genetic factors in PLWH with NAFLD is limited.
Objectives: This study aimed to investigate whether carriers of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314 had association with the risk of NAFLD, and whether PLWH with NAFLD also had similar genetic risk factors as those with NAFLD alone.
Methods: These single nucleotide polymorphisms (SNPs) were determined by using TaqMan allelic discrimination performed and analyzed by the Applied Biosystem platform in blood samples of 142 healthy individuals, 136 NAFLD patients, and 253 PLWH with NAFLD.
Results: The genotype distributions of PNPLA3 rs738409 (CC vs. GG genotypes) was significantly different among the groups (P < 0.05), while no significant differences were found for the TM6SF2 rs58542926 and HSD17B13 rs6834314 genotype. The NAFLD group showed a higher frequency of PNPLA3 GG genotype compared to healthy controls, associated with increased odds of NAFLD (OR 3.8; 95% CI 1.7 - 8.3). Comparing the NAFLD and PLWH with NAFLD groups, the NAFLD group had higher frequencies of CG and GG genotypes of PNPLA3 and lower frequency of GG genotype of HSD17B13. The multivariate analysis revealed several factors that remained significantly different between the two groups, including age, controlled attenuated parameter, body mass index, alanine aminotransferase, high-density lipoprotein, gender, PNPLA3 GG genotype, and HSD17B13 GG genotype.
Conclusion: PNPLA3 rs738409 was associated with NAFLD development while other SNPs were not significantly associated with NAFLD. The genotypes for PLWH with NAFLD were not significantly different from healthy controls.
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