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- Mancina, Rosellina Margherita, et al.
(författare)
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A two gene-based risk score predicts alcoholic cirrhosis development in males with at-risk alcohol consumption
- 2019
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Ingår i: Application of Clinical Genetics. - 1178-704X. ; 12, s. 1-10
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Tidskriftsartikel (refereegranskat)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 x 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI x 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.
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| 2. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis
- 2014
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Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 34:4, s. 514-520
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence. A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested. A higher incidence of alcoholic cirrhosis was observed in individuals with an older (>= 24years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value<0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value<0.001). Both age at onset of at-risk alcohol consumption and PNPLA3148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value<0.001; 1.53(1.07-2.19), P-value=0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38). Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence.
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