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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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- Pirazzi, Carlo, et al.
(författare)
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High prevalence of genetic determined familial hypercholesterolemia in premature coronary artery disease.
- 2019
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Ingår i: The application of clinical genetics. - 1178-704X. ; 12, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- Background: Premature coronary artery disease (CAD) is a major cause of mortality and morbidity. Increased low-density lipoprotein-cholesterol (LDL-C) level is a major risk factor for CAD and thus the main target for its prevention. Familial Hypercholesterolemia (FH) is a genetic inherited disorder characterized by high LDL-C, and subsequent premature CAD development. Early drug treatment with lipid-lowering medications in FH prevents cardiovascular disease onset. The FH prevalence in the Northern European general population is 0.3%, and it is estimated that it explains 20% of premature CAD cases in individuals with familial clustering. Despite the wide number of papers showing the prevalence of clinical FH in cardiovascular disease, the prevalence of genetic FH in individuals with premature CAD is not yet well known. Here, we examined the prevalence of genetically determined FH in individuals with premature CAD. Patients and methods: 66 patients who underwent coronary angiography with suspected premature acute coronary syndrome (age <50 years for men and <55 years for women) underwent genetic screening to identify FH-causing mutations. All patients underwent physical and clinical examinations. Information about family and personal history, drug therapy and habits were also collected. Results: We found FH-causative mutations in 3/66 (4.5%) screened individuals with premature CAD. When considering individuals with confirmed CAD after coronary angiography, the FH mutation prevalence was 6.1% (3/49). After excluding individuals with classical risk factors for CAD other than hypercholesterolemia, the FH mutation prevalence raised to 15.8% (3/19). Conclusion: In conclusion, we found that individuals with premature CAD have a more than 15-fold increased prevalence of FH mutations compared to the general population.
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