PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population.
OBJECTIVE
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).


CONCLUSIONS
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.
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Juozas
J
Kupcinskas
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Irena
I
Valantiene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Greta
G
Varkalaitė
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Ruta
R
Steponaitiene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jurgita
J
Skieceviciene
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jolanta
J
Sumskiene
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Vitalija
V
Petrenkiene
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jurate
J
Kondrackiene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Gediminas
G
Kiudelis
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Frank
F
Lammert
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. l.kupcinskas@gmail.com.
Limas
L
Kupcinskas
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D013381:Subtilisins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000076202:c-Mer Tyrosine Kinase; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008049:Lipase; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D013381:Subtilisins; D044767:Ubiquitin-Protein Ligases; D000076202:c-Mer Tyrosine Kinase; C118307:RNF7 protein, human; C097072:MERTK protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent; C099101:PCSK7 protein, human