6533b850fe1ef96bd12a857f
RESEARCH PRODUCT
The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B.
Thomas BergSalvatore PettaAndre BoonstraChristopher LiddleHenry Lik-yuen ChanMaria Lorena AbateWillem P. BrouwerJacob GeorgeMaiiada Hassan NazmyVincent Wai-sun WongJanett FischerMohammed EslamAlessandra MangiaKhaled Thabetsubject
0301 basic medicineLiver CirrhosisMaleAlcoholic liver diseaseCirrhosisSex FactorSeverity of Illness IndexCohort StudiesGene FrequencyFibrosisNon-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver diseaseAge FactorProspective StudiesChronicMembrane ProteinMultivariate AnalysiAge FactorsHepatitis CSingle NucleotideMiddle AgedHepatitis BPrognosisHepatocellular carcinomaDisease ProgressionFemaleHumanAdultmedicine.medical_specialtyLogistic ModelPrognosiAcyltransferaseLiver CirrhosiAcetyltransferases; Acyltransferases; Adult; Age Factors; Cohort Studies; Confidence Intervals; Disease Progression; Female; Gene Frequency; Genetic Predisposition to Disease; Hepatitis B Chronic; Humans; Liver Cirrhosis; Logistic Models; Male; Membrane Proteins; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Polymorphism Single Nucleotide; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Sex FactorsPolymorphism Single NucleotideRisk Assessment03 medical and health sciencesHepatitis B ChronicSex FactorsSDG 3 - Good Health and Well-beingAcetyltransferasesInternal medicineAcetyltransferasemedicineConfidence IntervalsHumansGenetic Predisposition to DiseasePolymorphismHepatologybusiness.industryMembrane ProteinsHepatologymedicine.diseaseMinor allele frequencyProspective Studie030104 developmental biologyLogistic ModelsImmunologyMultivariate AnalysisCohort StudiebusinessConfidence IntervalAcyltransferasesdescription
Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patients underwent gene expression analysis to assess the functional consequences of rs641738 on hepatic MBOAT7 expression. The minor allele (T) of rs641738 was associated with greater inflammation (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.95; P = 0.001) and fibrosis (OR = 1.31; 95% CI, 1.19-1.92; P = 0.01). Risk allele frequency in whites (0.43) was greater than in Chinese (0.24), translating to a larger size effect in the former. The rs641738 (T) allele was associated with lower hepatic MBOAT7 expression (P = 0.008), and the latter was associated with serum liver enzymes and inflammation. Neither patatin-like phospholipase domain-containing protein 3 rs738409 nor transmembrane 6 superfamily member 2 rs58542926 polymorphisms influenced disease severity. Conclusion: In patients with CHB, MBOAT7 rs641738 influences hepatic inflammation and fibrosis stage. (Hepatology 2017;65:1840-1850).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 | Hepatology (Baltimore, Md.) |