Analysis of human leukocyte antigen allele polymorphism in patients with non alcoholic fatty liver disease

Karrar, Azza; Hariharan, Siddharth; Fazel, Yousef; Moosvi, Ali; Houry, Mohamad; Younoszai, Zahra; Jeffers, Thomas L.; Li, Zheng; Otgonsuren, Munkhzul; Hunt, Sharon; Monge, Fanny; Goodman, Zachary; Younossi, Zobair M.

doi:10.1097/md.0000000000016704

Cited by 9 publications

(8 citation statements)

References 32 publications

(29 reference statements)

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“…To clarify how it affects the pathogenesis of NAFLD, we evaluated the association between the B*54:01 allele and microbiome. Some reports have shown that particular HLA alleles are associated with NAFLD, (41,42) but we have no knowledge about the pathogenic roles of HLA alleles in NAFLD development. One possibility is HLA affects liver injury through the immune system directly, and another is that HLA might regulate NAFLD indirectly through the microbiome.…”

Section: Discussionmentioning

confidence: 97%

Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus

et al. 2020

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Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two-stage analysis to identify NAFLD-associated loci in Japanese patients. In stage I, 275 metabolically healthy normal-weight patients with NAFLD were compared with 1,411 non-NAFLD controls adjusted for age, sex, and alcohol consumption by a genomewide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E-08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E-07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E-07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E-07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non-NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11-1.28; P = 2.10E-06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04-1.27; P = 6.19E-03) with increased NAFLD risk. Imputation-based typing of HLA showed a significant difference in the distribution of HLA-B, HLA-DR-beta chain 1 (DRB1), and HLA-DQ-beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next-generation sequence-based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA-B allele distribution and the significant increase of the HLA-B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta-diversity analysis of rs2076529 and HLA-B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA-B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. (Hepatology Communications 2020;4:1124-1135). N onalcoholic fatty liver disease (NAFLD) is defined as liver steatosis without alcoholic liver injury and other liver disease from apparent pathogenic factors, e.g., pharmacological. The global prevalence of NAFLD was estimated at 25.2% by a recent systematic review. (1) The number of patients with NAFLD is increasing annually due to the gradual increment in the prevalence of metabolic syndrome. (2)

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Section: Discussionmentioning

confidence: 97%

Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus

et al. 2020

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“…24 In a study of 85 adults with biopsy-proven NAFLD, investigators performed genetic testing to explore associations between HLA haplotypes and disease severity. 25…”

Section: Discussionmentioning

confidence: 99%

“…The majority of pediatric AIH is associated with HLA‐DRB1*0301 24 . In a study of 85 adults with biopsy‐proven NAFLD, investigators performed genetic testing to explore associations between HLA haplotypes and disease severity 25 . HLA‐DRB1*03 was associated with an increased risk of NASH, while HLA‐B*27 was associated with severe steatosis.…”

Section: Discussionmentioning

confidence: 99%

Significance of autoantibody seropositivity in children with obesity and non‐alcoholic fatty liver disease

et al. 2020

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Background: Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children. Objective: To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity. Methods: Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ 2 testing, and multivariable logistic regression was used for binary or ordinal outcomes. Results: One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups. Conclusions: Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.

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“…The genetic connection between the variables in the pathogenesis of NAFLD and NASH developments has been concerned (Karrar et al, 2019). Earlier studies showed that NAFLD could exist in the nonobese subjects of 10-20%, most frequently associated with central adiposity, recent weight gain, and genetic risk factors (Namjou et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Effect of angiotensin converting enzyme gene studies in nonalcoholic fatty liver disease subjects

Al‐Otaiby¹

2020

Int. j. adv. appl. sci.

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Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. ACE gene is the key to involve with transforming Angiotensin-I to the potent vasoconstrictor of angiotensin-II, well-known for the association with all the above-mentioned diseases. Limited studies have been documented with NAFLD and ACE gene I/D polymorphism in the global studies, and there are no studies that have been documented in the Saudi population. The aim of the current study was to investigate the genetic association between angiotensin converting enzyme (ACE) gene, insertion (I)-deletion (D) polymorphisms in NAFLD in the Saudi population. NAFLD is a clinic pathological syndrome produced due to the environment, genetic, and metabolic stress-correlated factors, which are demonstrated clinically as fat accumulation in hepatocytes. This is a hospitalbased case-control study implemented in 95 NAFLD cases and 78 non-NAFLD subjects. Genomic DNA was extracted in all the subjects to perform the PCR with ACE gene I/D polymorphism, and the current study results revealed the negative association between the NAFLD cases and controls in the Saudi population (DD vs II; OR-0.17: 95% CI (0.04-0.64), p=0.04, DD+ID vs II: OR-0.19; 95% CI (0.05-0.70), p=0.006 and D vs I; OR-0.34: 95%CI (0.21-0.57), p=0.003. In conclusion, this study confirms NAFLD has no genetic role in the Saudi population with ACE gene I/D polymorphism analysis.

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Analysis of human leukocyte antigen allele polymorphism in patients with non alcoholic fatty liver disease

Cited by 9 publications

References 32 publications

Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus

Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus

Significance of autoantibody seropositivity in children with obesity and non‐alcoholic fatty liver disease

Effect of angiotensin converting enzyme gene studies in nonalcoholic fatty liver disease subjects

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