Therefore, we investigated the impact of MetS, PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 on overall and cardiovascular disease (CVD) specific mortality among subjects with or without NAFLD.
Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound <i>O</i>-acyltransferase domain-containing 7 (<i>MBOAT7</i>) and transmembrane channel-like 4 (<i>TMC4</i>) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017).
In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis.
A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers.
Furthermore, multivariable logistic regression analysis adjusted for biologically relevant covariates and potential confounders associated with the risk of liver disease progression revealed that MBOAT7 rs641738 is not associated either with fibrosis progression in CHC group (OR = 1.12; 95% CI: 0.55-2.28; p = 0.761) or with chronic progressive state in CHB patients (OR = 0.81; 95% CI: 0.41-1.61; p = 0.547).
The development of HCC was independently associated with PNPLA3 rs738409 (OR<sub>adjusted</sub> 1.84 [95% CI 1.55-2.18], p = 1.85 × 10<sup>-12</sup>) and TM6SF2 rs58542926 (OR<sub>adjusted</sub> 1.66 [1.30-2.13], p = 5.13 × 10<sup>-05</sup>), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR<sub>adjusted</sub> 1.04 [0.88-1.24], p = 0.61) was not significant.
We determined the frequency of PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624), TM6SF (rs8542926), LYPLAL1 (rs12137855) and MBOAT7 (rs626283) by RT-PCR in 117 HIV-positive patients on cART and stratified participants based on their "controlled attenuation parameter" (CAP) into probable (CAP: 215-300 dB/m) and definite (CAP >300 dB/m) hepatic steatosis.
In contrast, MBOAT7 rs641738 variants, neither heterozygous nor homozygous genotypes, were not associated with hepatic steatosis, insulin resistance, lipid levels and liver enzymes.
Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound <i>O</i>-acyltransferase domain-containing 7 (<i>MBOAT7</i>) and transmembrane channel-like 4 (<i>TMC4</i>) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017).
The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors.
Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound <i>O</i>-acyltransferase domain-containing 7 (<i>MBOAT7</i>) and transmembrane channel-like 4 (<i>TMC4</i>) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017).
We conclude that the variant MBOAT7 rs641738 genotype is not associated with spontaneous clearance of HBV and HCV infections or with the progression of liver disease in chronic hepatitis B or C in a genetic context of Mediterranean patients.
Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491).
We conclude that the variant MBOAT7 rs641738 genotype is not associated with spontaneous clearance of HBV and HCV infections or with the progression of liver disease in chronic hepatitis B or C in a genetic context of Mediterranean patients.
We genotyped MBOAT7 rs641738 polymorphism in 971 consecutive Moroccan subjects, including 288 patients with chronic hepatitis C (CHC), 98 cases with spontaneous clearance of HCV, 268 patients with chronic hepatitis B (CHB), 126 spontaneously cleared HBV infections and 191 healthy controls.
The development of HCC was independently associated with PNPLA3 rs738409 (OR<sub>adjusted</sub> 1.84 [95% CI 1.55-2.18], p = 1.85 × 10<sup>-12</sup>) and TM6SF2 rs58542926 (OR<sub>adjusted</sub> 1.66 [1.30-2.13], p = 5.13 × 10<sup>-05</sup>), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR<sub>adjusted</sub> 1.04 [0.88-1.24], p = 0.61) was not significant.