PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population download Full Article (PDF file)
Juozas Kupcinskas1,2,*, Irena Valantiene1,2,*, Greta Varkalaitė1, Ruta Steponaitiene1, Jurgita Skieceviciene1, Jolanta Sumskiene2, Vitalija Petrenkiene2, Jurate Kondrackiene2, Gediminas Kiudelis1,2, Frank Lammert3, Limas Kupcinskas1,2
1) Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas;
2) Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
3) Department of Medicine II, Saarland University Medical Center, Homburg, Germany
ABSTRACT Background & Aims: Genome-wide association studies have revealed an association between the risk of developing liver fibrosis or cirrhosis and the single nucleotide polymorphisms (SNPs) of the PNPLA3, RNF7, MERTK and PCSK7 genes. We aimed to validate these results in an Eastern European population. Methods: We evaluated the associations between the PNPLA3 (rs738409), RNF7 (rs16851720), MERTK (rs4374383) and PCSK7 (rs236918) variants and liver fibrosis and cirrhosis in a series of consecutive patients recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, during the period 2012-2015. The study included 317 individuals with liver cirrhosis, 154 individuals with liver fibrosis, and 498 controls. The studied SNPs were determined using RT-PCR TaqMan assays. Results: MERTK and PCSK7 SNPs were not associated with liver fibrosis or cirrhosis. The PNPLA3 SNP rs738409 was associated with a higher risk of developing liver fibrosis (aOR: 1.65, P=0.001) and cirrhosis (aOR: 1.92, P=5.57*10-7). PNPLA3 genotypes were also associated with higher risk of developing liver fibrosis and cirrhosis in dominant (aOR: 1.98, P=2.20*10-5; aOR: 1.67, P=0.008, respectively) and recessive (aOR: 3.94, P=5.16*10-5; aOR: 3.02, P=0.003, respectively) models. RNF7 rs16851720 was associated with liver cirrhosis comparing CC vs. AA + CA genotypes (aOR: 0.26, P=0.020). Conclusion: Our study showed that PNPLA3 rs738409 and RNF7 rs16851720 confer an increased risk of developing liver fibrosis and cirrhosis in this Eastern European population, while the MERTK and PCSK7 SNPs are not associated with these conditions. Key words: PNPLA3 – RNF7 – MERTK – PCSK7 – liver cirrhosis – liver fibrosis – SNP – gene polymorphism. Abbreviations: GWAS: Genome-wide association studies; HBV: hepatitis B virus; HCV: hepatitis C virus; HH: hereditary hemochromatosis; MERTK: proto-oncogene tyrosine-protein kinase MER; NAFLD: non-alcoholic fatty liver disease; PCSK7: proprotein convertase 7; PNPLA3: patatin-like phospholipase domain containing 3; RNF7: SAG sensitive to apoptosis gene; SNP: single nucleotide polymorphism.