Abstract:Hepatic steatosis can occur with any antiretroviral therapy (cART). Although single nucleotide polymorphisms (SNPs) have been identified to predispose to alcoholic and non-alcoholic fatty liver disease, their role for treatment-associated steatosis in HIV-positive patients remains unclear. 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… Show more
“…In conclusion, the rs641738 is not associated with NAFLD in our population. The association of the variant and NAFLD as disease trait could not be replicated in population-based or hospital based studies from Asia 16 – 18 , 20 or Germany 14 . Nevertheless, the association with liver histology, including fibrosis was only observed in patients with NAFLD of European ancestry 12 – 14 ; this finding could not be replicated in studies that included Asian population 16 , 17 .…”
Section: Discussionmentioning
confidence: 91%
“…Meanwhile this manuscript was under the peer review process, several reports on the role of rs641738 were published 16 – 18 , 20 ; specifically, there were large studies that included well characterized patients diagnosed by liver biopsy 16 , 17 . Interestingly, these studies showed a negative association of the variant with NAFLD 16 – 18 , 20 and NASH or liver fibrosis 16 , 17 .…”
Section: Discussionmentioning
confidence: 99%
“…NAFLD diagnosed by liver ultrasonographic examination No evidence of association No evidence of association with liver enzymes Koo BK, 2017 17 Korea, Asian descent. Case-control hospital based 525 individuals (416 patients with NAFLD diagnosed by liver biopsy and 109 healthy controls) No evidence of association No evidence of association with NASH, fibrosis, or liver enzymes Dold L, 2017 20 Germany, Caucasian descent Case-control hospital based 291 individuals (142 HIV-infected patients and 149 healthy blood donors). Liver stiffness assessed by Fibroscan and NAFLD by liver ultrasound.…”
Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84–99% power if an additive genetic model is assumed for estimated odds ratios of 1.3–1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
“…In conclusion, the rs641738 is not associated with NAFLD in our population. The association of the variant and NAFLD as disease trait could not be replicated in population-based or hospital based studies from Asia 16 – 18 , 20 or Germany 14 . Nevertheless, the association with liver histology, including fibrosis was only observed in patients with NAFLD of European ancestry 12 – 14 ; this finding could not be replicated in studies that included Asian population 16 , 17 .…”
Section: Discussionmentioning
confidence: 91%
“…Meanwhile this manuscript was under the peer review process, several reports on the role of rs641738 were published 16 – 18 , 20 ; specifically, there were large studies that included well characterized patients diagnosed by liver biopsy 16 , 17 . Interestingly, these studies showed a negative association of the variant with NAFLD 16 – 18 , 20 and NASH or liver fibrosis 16 , 17 .…”
Section: Discussionmentioning
confidence: 99%
“…NAFLD diagnosed by liver ultrasonographic examination No evidence of association No evidence of association with liver enzymes Koo BK, 2017 17 Korea, Asian descent. Case-control hospital based 525 individuals (416 patients with NAFLD diagnosed by liver biopsy and 109 healthy controls) No evidence of association No evidence of association with NASH, fibrosis, or liver enzymes Dold L, 2017 20 Germany, Caucasian descent Case-control hospital based 291 individuals (142 HIV-infected patients and 149 healthy blood donors). Liver stiffness assessed by Fibroscan and NAFLD by liver ultrasound.…”
Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84–99% power if an additive genetic model is assumed for estimated odds ratios of 1.3–1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
“…First, there are limited studies that have characterized the distribution and associations of PNPLA3 polymorphisms in those with HIV in the U.S. population which is ethnically and racially different from studies in European populations. 12,13 Second, some investigators have speculated that disease progression and injury would be greater in those with risk for NASH combined with HCV infection. Indeed, a recent meta-analysis suggested that the GG allele was highly associated with the risk of advanced liver fibrosis and steatosis in Caucasian populations with chronic HCV infection.…”
The HRM method is an effective, rapid technique for characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry gene polymorphisms associated with the development of NASH or ASH. Prospective studies should focus on this group to determine whether they represent a subset of HIV-infected persons at increased risk of fibrotic progression.
BackgroundPolymorphisms have been identified to predispose to NAFLD. Here, we accessed the seven polymorphisms of rs1260326, rs780094 in GCKR, rs2954021 near TRIB1, rs2228603 in NCAN, rs58542926 in TM6SF2, rs12137855 near LYPLAL1, and rs10883437 near CPN1 on NAFLD susceptibility in the Uygur population.Material and methodsWe collected 620 samples (317 NAFLD and 303 controls) for this case-control study. Meta-analysis was performed using Stata Software.ResultsOur data detected that the rs1260326 (T vs. C: OR = 1.27, 95% CI = 1.01–1.59) and rs780094 (T vs. C: OR = 1.30, 95% CI = 1.04–1.63) were significantly associated with the susceptibility to NAFLD in Uygur population. The rs1260326 and rs780094 T/T genotype are significantly associated with soda, egg, and soybean intakes in the consumption group with twice or more in a week. Furthermore, a significant haplotype effect of rs1260326/T- rs780094/T was found (OR = 1.29, 95% CI: 1.03–1.62) compared with CC haplotype. An additional meta-analysis using 4352 cases and 10,168 controls established that rs780094 (OR = 1.21, 95%CI: 1.14–1.28) is significantly associated with NAFLD. Finally, among the 4 case-control studies on rs1260326, including 712 NAFLD and 658 controls, significant associations were found in Asian, liver biopsy, adult and pediatric groups.ConclusionCollectively, both our case-control study and meta-analysis confirm a significant association between rs780094 and NAFLD. Additionally, our results suggest Asian-specific, liver biopsy-specific, adult-specific and pediatric-specific associations between the rs1260326 and NAFLD. Moreover, the rs1260326 and rs780094 T/T genotype are significantly associated with food habits, such as soda, egg, and soybean.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0877-3) contains supplementary material, which is available to authorized users.
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