Association of genetic variants in PNPLA3, MERTK, PCSK7 and RNF7 with liver cirrhosis
| Author | Affiliation |
|---|---|
| Date |
|---|
2015-05-14 |
Abstract speech of authors were not edited.
Bibliogr.: p. 53
Background: Liver cirrhosis (LC) is a progressing disease commonly caused by alcohol consumption, infections of chronic hepatitis B and C and other. The search for genetic factors that could help to select patients at higher risk of developing LC is necessary. Current data indicate role of PNPLA3 gene product in lipid homeostasis and genome-wide association studies (GWAS) revealed PNPLA3 (rs738409) single-nucleotide polymorphism (SNP) association with liver diseases and fibrosis risk [3]. A recent GWAS suggest a possible relationship between the clearance of apoptotic cells and liver fibrosis, revealing genetic polymorphisms of MERTK (rs4374383) and RNF7 (rs16851720) importance [1]. Other GWAS demonstrated that PSCK7 (rs236918) is a risk factor of LC in hereditary hemochromatosis (HH) patients [2,4]. Correlation of these SNPs with LC has not been studied well. The aim was to perform genotyping for PNPLA3 (rs738409), MERTK (rs4374383), PCSK7 (rs236918) and RNF7 (rs16851720) in LC patients and healthy individuals groups and determine the potential link between these SNPs and the risk of developing LC. Materials and Methods: In total 244 patients with LC and 498 healthy control individuals were genotyped. Genotyping was performed for 4 genetic variants in PNPLA3, MERTK, PCSK7, RNF7 genes using real-time PCR TaqMan® assay. Statistical analysis were performed using PLINK: Whole genome data analysis toolset. Results: MERTK and PCSK7 SNPs was not associated with the risk of developing LC (adjusted odds ratio (ODa)-1,2, 95% confidence interval (CI95) 0,96-1,52, P-0,109; ODa-0,79, CI95 (0,56-1,11), P-1,69 respectively). RNF7 SNP showed no significant association in allelic association analysis (ODa-0,75, CI95 (0,56-1,28), P-0,074) and showed lower risk of developing LC when compared with CC genotype (ODa-0,18, CI95 (0,04-0,79), P-0,023). PNPLA3 SNP showed allelic association with higher risk of developing LC (ODa -1,91, CI95 (1,47-2,50), P-1,812*10-8), genotypic ass