Association of FXR gene variants with cholelithiasis - 05/02/15
, Simone Harsch a, ⁎ , Olga Renner a , Dominique Richter a , Oliver Müller b , Eduard F. Stange b Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Summary |
Background and aim |
Impairment of bile acid homeostasis is the most important risk factor of gallstone disease. Thereby the bile acid sensor farnesoid X receptor (FXR) plays a pivotal role in hepatic and intestinal bile acid metabolism. In this explorative study, the FXR gene was investigated to identify gene variants, associated with gallstone formation in a Caucasian population.
Methods |
Sequencing of the FXR gene was conducted in a randomly selected cohort of gallstone carriers (n=30) and control subjects (n=16) from Stuttgart, Germany. Genomic DNA was obtained from blood leukocytes. Genotype frequencies were established in the total cohort (controls: n=133, gallstone carriers: n=74). For expression analysis, total RNA and protein were isolated from ileal biopsies.
Results |
The sequencing showed the sole appearance of 10 SNPs in gallstone carriers. Further genotype analysis revealed significant gender- and weight-dependent frequency differences of 3 SNPs between gallstone carriers and controls in males (rs35724: OR=4.73, P=0.022) and normal weight subjects (rs11110385: OR=3.67, P=0.027; rs11110386: OR=3.67, P=0.027) applying the 11+12<>22 allele model. Furthermore, rs11110385 carriers showed a significantly decreased FXR protein expression (11+12<>22: P=0.003). Significant mRNA expression differences between lean rs11110385 carriers and non-carriers were observed in FXR target genes (decrease: ILBP: P=0.042, OSTalpha: P=0.071, FGF19: P=0.011. Increase: LRH1: P=0.044).
Conclusions |
Three FXR gene variants (rs35724, rs11110385, rs11110386) were identified as potential susceptibility factors for cholelithiasis in a German cohort in gender- and weight-dependent manners. Thereby the tag SNP rs11110385 seemed to influence the activation of the FXR gene.
Le texte complet de cet article est disponible en PDF.Abbreviations : ABCB4, ABCB11, ABCG5/G8, ADRB3, ASBT, BA, BMI, bp, CI, CYP7A1, CYP7B1, FGF, FXR, GWAS, HWE, ILBP, LD, LRH1, MALDI-TOF MS, NTCP, OR, Ostα/β, RT-qPCR, SEM, SHP, SNP
Plan
Vol 39 - N° 1
P. 68-79 - février 2015 Retour au numéro
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