The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease
| Autor: | Gustavo Osvaldo Castaño, Silvia Cristina Sookoian, Maria Soledad Rosselli, Carlos José Pirola, Tomás Fernández Gianotti, Adriana Laura Burgueño |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Nonalcoholic steatohepatitis Receptors Steroid medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Genotype Genética Humana Biology Polymorphism Single Nucleotide Internal medicine Nonalcoholic fatty liver disease Genetics medicine Humans General Pharmacology Toxicology and Pharmaceutics genes Molecular Biology Gene Genetic Association Studies Genetics (clinical) Liver injury Pregnane X receptor Haplotype Pregnane X Receptor nutritional and metabolic diseases Middle Aged medicine.disease digestive system diseases Fatty Liver Medicina Básica Cross-Sectional Studies Endocrinology Haplotypes Liver Nuclear receptor Case-Control Studies Molecular Medicine Female Chemical and Drug Induced Liver Injury Pharmacogenetics |
| Zdroj: | Pharmacogenetics and Genomics. 20:1-8 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0b013e328333a1dd |
| Popis: | Objective To explore the contribution of gene variants and derived haplotypes of the pregnane X receptor (NR1I2) to the severity of nonalcoholic fatty liver disease (NAFLD). Methods A total of 290 individuals were evaluated in a case-control association study, including 188 NAFLD patients with different stages of disease severity and 102 healthy individuals. Four tag single nucleotide polymorphisms (SNPs; rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3 and representing 33 polymorphic sites (r 2> 0.8) were genotyped. Four additional SNPs (rs3814055, rs3814057, rs6785049, and rs7643645) were also included because they showed earlier evidence of functionality. Results Genotypic tests for single SNPs showed that rs7643645 and rs2461823 were significantly associated with disease severity by ordinal multinomial analysis (P < 0.0015 and 0.039, respectively). A significant association was also observed under the additive model for both variants (P < 0.00038 and 0.012, respectively). Consistent with the analysis of individual markers, we observed that the multimarker composed of rs2461823/ A-rs7643645/G was significantly associated with disease severity (P< 6.9 10– 5, b: 0.45). In addition, the rs7643645/ G variant was significantly associated with ALT level (P < 0.026), a surrogate marker of severe liver injury. Finally, in univariate analysis rs7643645/G was significantly associated with fatty liver disease (P < 0.04), with an odds ratio of 1.457 (95% confidence interval: 1.018–2.086). Conclusion Our study suggests that pregnane X receptor polymorphisms and related haplotypes may contribute to disease severity in NAFLD by influencing the individual susceptibility to progress to more severe stages of the disease. Fil: Sookoian, Silvia Cristina. Laboratorio de hepatología clínica y molecular; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castaño, Gustavo Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina Fil: Burgueño, Adriana Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gianotti, Tomas Fernández. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Rosselli, Maria Soledad. Laboratorio de hepatología clínica y molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pirola, Carlos José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
| Databáze: | OpenAIRE |
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