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

基于两种基因的风险评分可预测有饮酒风险的男性发生酒精性肝硬化的可能性

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作者:Rosellina Margherita Mancina, Flaminia Ferri, Alessio Farcomeni, Antonio Molinaro, Angela Maffongelli, Monica Mischitelli, Edoardo Poli, Lucia Parlati, Maria Antonella Burza, Adriano De Santis, Fabio Attilia, Claudia Rotondo, Maria Margherita Rando, Maria Luisa Attilia, Mauro Ceccanti, Stefano Ginan

Background

Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and

Conclusion

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

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.

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