Association between promoter and coding region mutations of UDP-glucuronosyltransferase 1A1 and β-thalassemia/Hb E with cholelithiasis

Background and objectives:  Cholelithiasis has been observed with high incidence in beta-thalassemia/hemoglobin E (β-thal/Hb E). Recent studies have shown that a variant TATA-box in the promoter region of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene is associated with the development of cholelithiasis. The coding region mutation (G71R) of the UGT1A1 gene was higher in Asians than those in Caucasians. The relationship between the variant UGT1A1 promoter and coding region gene and cholelithiasis in β-thal/Hb E subjects were investigated. Methods:  One hundred and seventeen β-thal/Hb E subjects entered this study. The TATA-box and G71R mutations were analyzed by fragment size analysis and restriction fragment length polymorphism methods, respectively. Results:  The incidence of cholelithiasis was higher in heterozygous (68.3%) and homozygous (100%) subjects compared with normal UGT1A1 haplotype (61.4%). Total bilirubin level (6.0 ± 2.03 mg/dL) in the homozygous group was significantly higher than that of wild type (3.31 ± 1.83 ng/dL). Prevalence of cholelithiasis increased with age (OR = 1.1, 95% CI = 1.03–1.12, P < 0.001). Female gender (OR = 3.7, 95% CI = 1.3–10.6, P < 0.01) and elevated liver enzyme (OR = 1.02, 95%CI = 1.0–1.04, P < 0.02) were two other risk factors for cholethiasis in β-thal/Hb E. Conclusion:  This study shows that the combined TATA-box variants and G71R mutations of the UGT1A1 is associated with cholelithiasis in β-thal/Hb E.