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Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study.
Can J Gastroenterol Hepatol. 2018; 2018:7564835.CJ

Abstract

Background & Aims

Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis.

Methods

Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped.

Results

One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis.

Conclusions

The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.

Authors+Show Affiliations

Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Laboratory of Pathology of The National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy.Hepatology Outpatient Clinic, Colleferro Hospital, Rome, Italy.Hepatology Outpatient Clinic, Colleferro Hospital, Rome, Italy.Liver Disease Unit, San Camillo-Forlanini Hospital, Rome, Italy.Liver Disease Unit, San Camillo-Forlanini Hospital, Rome, Italy.Laboratory of Microscopic and Ultrastructural Anatomy, CIR, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Laboratory of Pathology of The National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy.University La Sapienza of Rome, Rome, Italy.Laboratory of Microscopic and Ultrastructural Anatomy, CIR, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29732362

Citation

Vespasiani-Gentilucci, Umberto, et al. "Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: a Proof of Concept Study." Canadian Journal of Gastroenterology & Hepatology, vol. 2018, 2018, p. 7564835.
Vespasiani-Gentilucci U, Dell'Unto C, De Vincentis A, et al. Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study. Can J Gastroenterol Hepatol. 2018;2018:7564835.
Vespasiani-Gentilucci, U., Dell'Unto, C., De Vincentis, A., Baiocchini, A., Delle Monache, M., Cecere, R., Pellicelli, A. M., Giannelli, V., Carotti, S., Galati, G., Gallo, P., Valentini, F., Del Nonno, F., Rosati, D., Morini, S., Antonelli-Incalzi, R., & Picardi, A. (2018). Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study. Canadian Journal of Gastroenterology & Hepatology, 2018, 7564835. https://doi.org/10.1155/2018/7564835
Vespasiani-Gentilucci U, et al. Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: a Proof of Concept Study. Can J Gastroenterol Hepatol. 2018;2018:7564835. PubMed PMID: 29732362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study. AU - Vespasiani-Gentilucci,Umberto, AU - Dell'Unto,Chiara, AU - De Vincentis,Antonio, AU - Baiocchini,Andrea, AU - Delle Monache,Marco, AU - Cecere,Roberto, AU - Pellicelli,Adriano Maria, AU - Giannelli,Valerio, AU - Carotti,Simone, AU - Galati,Giovanni, AU - Gallo,Paolo, AU - Valentini,Francesco, AU - Del Nonno,Franca, AU - Rosati,Davide, AU - Morini,Sergio, AU - Antonelli-Incalzi,Raffaele, AU - Picardi,Antonio, Y1 - 2018/03/14/ PY - 2017/11/10/received PY - 2018/01/23/revised PY - 2018/02/15/accepted PY - 2018/5/8/entrez PY - 2018/5/8/pubmed PY - 2019/3/5/medline SP - 7564835 EP - 7564835 JF - Canadian journal of gastroenterology & hepatology JO - Can J Gastroenterol Hepatol VL - 2018 N2 - Background & Aims: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis. Methods: Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped. Results: One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis. Conclusions: The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics. SN - 2291-2797 UR - https://www.unboundmedicine.com/medline/citation/29732362/Combining_Genetic_Variants_to_Improve_Risk_Prediction_for_NAFLD_and_Its_Progression_to_Cirrhosis:_A_Proof_of_Concept_Study_ L2 - https://dx.doi.org/10.1155/2018/7564835 DB - PRIME DP - Unbound Medicine ER -