A two gene-based risk score predicts alcoholic cirrhosis development in males with at-risk alcohol consumption.

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 () rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 () rs58542926, membrane bound O-acyltransferase domain containing 7 () rs641738, and cluster of differentiation 14 () 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 , , , and 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 , , and were associated with alcoholic cirrhosis prevalence. and were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of allele T) + (number of 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.