Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 12, 1-10
eCollection

A Two Gene-Based Risk Score Predicts Alcoholic Cirrhosis Development in Males With At-Risk Alcohol Consumption

Affiliations

A Two Gene-Based Risk Score Predicts Alcoholic Cirrhosis Development in Males With At-Risk Alcohol Consumption

Rosellina Margherita Mancina et al. Appl Clin Genet.

Abstract

Background: Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption.

Materials and methods: A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves.

Results: We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity.

Conclusion: We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.

Keywords: CD14; PNPLA3; alcoholic cirrhosis; predictive score.

Conflict of interest statement

Disclosure The authors reports no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Cumulative incidence of alcoholic cirrhosis in individuals according to (A) PNPLA3 I148M genotype and (B) CD14 C159T genotype. Alcohol years indicate the duration of at-risk alcohol consumption (daily intake of ≥3 alcohol units). It corresponds to the number of years from age at onset of at-risk alcohol consumption to age at cirrhosis onset or final follow-up without cirrhosis, measuring hence the period of exposure to the pathogenic agent. The number at the bottom indicates the number of individuals at risk at the following time points: 0, 10, 20, 30, and 40 years. Abbreviations: PNPLA3 II, individuals with two 148I alleles; MM, individuals with two 148M alleles; IM, heterozygotes; CD14 CC, individuals with two 159C alleles; TT, individuals with two 159T alleles; CT, heterozygotes.

Similar articles

See all similar articles

References

    1. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141(5):1572–1585. - PMC - PubMed
    1. Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(Suppl 1):2–6. - PubMed
    1. Masarone M, Rosato V, Dallio M, et al. Epidemiology and natural history of alcoholic liver disease. Rev Recent Clin Trials. 2016;11(3):167–174. - PubMed
    1. Heslin KC, Elixhauser A, Steiner CA. Identifying in-patient costs attributable to the clinical sequelae and comorbidities of alcoholic liver disease in a national hospital database. Addiction. 2017;112(5):782–791. - PubMed
    1. Day CP. Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. Liver Int. 2006;26(9):1021–1028. - PubMed
Feedback