RESUMEN
BACKGROUND & AIMS: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones. METHODS: Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.0×10(-7) (UGT1A1, SLCO1B1, LST-3TM12, SLCO1A2) were analyzed in 1018 individuals with known gallstone composition. Gallstone risk was analyzed in 2606 German choleystecomized individuals and 1121 controls and was replicated in 210 cases and 496 controls from South America. RESULTS: By using the presence of bilirubin as a phenotype, variants rs6742078 (UGT1A1; P = .003), rs4149056 (SLCO1B1; P = .003), and rs4149000 (SLCO1A2; P = .015) were associated with gallstone composition. In regression analyses, only UGT1A1 and SLCO1B1 were independently retained in the model. UGT1A1 (rs6742078; P = .018) was associated with overall gallstone risk. In a sex-stratified analysis, only male carriers of rs6742078 had an increased risk for gallstone disease (P = 2.1×10(-7); odds ratio(recessive), 2.34; P(women) = .47). The sex-specific association of rs6742078 was confirmed in samples from South America (P(men) = .046; odds ratio(recessive), 2.19; P(women) = .96). CONCLUSIONS: The UGT1A1 Gilbert syndrome variant rs6742078 is associated with gallstone disease in men; further studies are required regarding the sex-specific physiology of bilirubin and bile acid metabolism. Variants of ABCG8 and UGT1A1 are the 2 major risk factors for overall gallstone disease, they contribute a population attributable risk of 21.2% among men.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Bilirrubina/sangre , Cálculos Biliares , Enfermedad de Gilbert , Glucuronosiltransferasa/genética , Transportadores de Anión Orgánico/genética , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8 , Adulto , Femenino , Cálculos Biliares/epidemiología , Cálculos Biliares/genética , Cálculos Biliares/metabolismo , Predisposición Genética a la Enfermedad/epidemiología , Estudio de Asociación del Genoma Completo , Genotipo , Alemania/epidemiología , Enfermedad de Gilbert/epidemiología , Enfermedad de Gilbert/genética , Enfermedad de Gilbert/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , América del Sur/epidemiologíaRESUMEN
BACKGROUND: The management of coincidental detected gallbladder polyps (GP) is still nebulous. There are few published data regarding their long-term growth. Objective of the present study was to investigate the prevalence and growth of gallbladder polyps in a survey of unselected subjects from the general population of a complete rural community. METHODS: A total of 2,415 subjects (1,261 women; 1,154 men) underwent ultrasound examination of the gallbladder, in November 1996 as part of a prospective study. Subjects in whom GP were detected at the initial survey underwent follow-up ultrasound examinations after 30 and 84 months. RESULTS: At the initial survey gallbladder polyps were detected in 34 subjects (1.4%; females: 1.1%, range 14 to 74 years; males: 1.7%, range 19 to 63 years). Median diameter was 5 +/- 2.1 mm (range 2 to 10 mm) at the initial survey, 5 mm +/- 2.8 mm (range 2 to 12 mm) at 30 months and 4 +/- 2.3 mm (range 2 to 9 mm) at 84 months. At the time of first follow-up no change in diameter was found in 81.0% (n = 17), reduction in diameter in 4.8% (n = 1) and increase in diameter in 14.3% (n = 3). At the time of second follow-up no increase in polyp diameter was found in 76.9% (n = 10) and reduction in diameter in 7.7% (n = 1). No evidence of malignant disease of the gallbladder was found. CONCLUSION: Over a period of seven years little change was measured in the diameter of gallbladder polyps. There was no evidence of malignant disease of the gallbladder in any subject.