title: Fibroblast growth factor receptor 4 Gly388Arg  polymorphism associated with severity of gallstone disease in a Chinese  population.
abstract: The etiology of gallstone disease is multifactorial;  supersaturation of bile with cholesterol is a primary cause for gallstone  formation. In previous studies, we found that fibroblast growth factor receptor  4 (FGFR4) plays an important role in maintaining bile acid homeostasis by regulating  the expression of cholesterol 7α-hydroxylase (CYP7A1), a rate-limiting enzyme for bile  acid biosynthesis. The Gly388Arg (G-388R) polymorphism of FGFR4 affects  stabilization and activation of FGFR4. Consequently, we studied the FGFR4 gene  as a candidate gene for genetic susceptibility to gallstone disease. We found  that overexpression of FGFR4, especially the G-388R mutant of FGFR4,  inhibits luciferase activity of CYP7A1 reporter in HepG2 cells, indicating that  the G-388R mutant of FGFR4 may have greater inhibitory activity against  bile acid biosynthesis. To investigate the association of FGFR4 polymorphism  with gallstone disease, 117 patients with gallstone disease and 457 controls  were genotyped for FGFR4 polymorphism G-388R by PCR-RFLP. Although the  incidence of gallstone disease was not greater in patients with the FGFR4 RR  genotype, the ratio of gallstone patients with acute cholecystitis in the FGFR4 RR genotype (42%) was significantly higher than that in other genotypes of FGFR4 (P = 0.019). In conclusion, the FGFR4 polymorphism is a genetic risk  factor contributing to aggravation of gallstone disease.
authors.affiliation: Department of Hepatobiliary Pancreas and Vessel Surgery, Chenggong Hospital of Xiamen University, Xiamen, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: W J
authors.initials: WJ
authors.lastname: Li
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wan
authors.forename: C D
authors.initials: CD
authors.lastname: Yu
authors.forename: W G
authors.initials: WG
authors.lastname: Li
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China; D041881:Cholecystitis, Acute / Q000209:etiology; D002790:Cholesterol 7-alpha-Hydroxylase; D005260:Female; D042882:Gallstones / Q000150:complications / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics*
chemical_list: C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase; D051499:Receptor, Fibroblast Growth Factor, Type 4