Polymorphisms in UGT1A1 gene in thalassemic children with or without gallstone at Srinagarind Hospital

Abstract

The prevalence of gallstone in Northeast Thailand has been reported to be 20.0%. There are many factors involved in gallstone formation including sex, age, enzyme deficiency and increased hemolysis condition such as thalassemia which resulted in hyperbilirubinemia. Mutations in the UGT1A1 gene would lead to a high risk of gallstone formation. This study aimed to investigate two UGT1A1 polymorphisms; the (G71R) using allele specific PCR and the TATA box [A(TA)nTAA] at promoter using direct DNA sequencing and high-resolution melting analysis (HRM) in thalassemic children with and without gallstone at Srinagarind Hospital, Khon Kaen University. Study was done on 113 patients with average age of 14.7 ± 5.1 year including 48 males (42.5%) and 65 females (57.5%). Gallstone was found in 21 patients (18.6%). The G71R polymorphism was detected in 7 subjects (6.2%). For the polymorphism in promoter, the (TA)6/(TA)7 were detected in 4 of the 36 patients examined (11.1%). These polymorphisms were observed in patients with (n=2) and without (n=8) gallstone. It was found that gallstone was mostly found in β-thalassemia/Hb E patients followed by patients with Hb H disease, Hb H-CS disease, EABart's disease and CS EABart's diseases. All the 7 patients with G71R polymorphism are heterozygotes. This result indicates likely that both G71R and (TA)6/(TA)7 polymorphisms of UGT1A1 gene may not be related to gallstone formation in northeast Thai patients. This may be due to the young age of the patients since gallstone formation takes time. Nonetheless, our result indicates that screening for UGT1A1 polymorphisms in the patients may not be necessary.

Key words: Gallstone, UGT1A1, Polymorphism, Thalassemia