Single nucleotide polymorphism rs3732860 in the 3′‐untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese

• DOI: 10.1111/jgh.12089
• Publication Date: 2012-12-07T13:02:04Z
• Authors: Jian Qin; Tian‐Quan Han; Wen‐Tao Yuan; Jing Zhang; Jian Fei; Zhao‐Yan Jiang; Zhen‐Min Niu; Kai‐Yue Zhang; Qi Hua; Xing‐Xing Cai; Shi‐Jie Xu; Wei Huang; Sheng‐Dao Zhang
• Keywords: Adult; Male; 0301 basic medicine; Genotype; Genetic Linkage; Gallstones; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Asian People; Cytochrome P-450 Enzyme System; Case-Control Studies; Humans; Female; Genetic Predisposition to Disease; 3' Untranslated Regions; Sequence Analysis; Alleles; Aged; DNA Primers; Genome-Wide Association Study

AbstractBackground and AimsGallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese.MethodsA genome‐wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α‐hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD.ResultsThree loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late‐onset patients. The single nucleotide polymorphism rs3732860 in the 3′‐untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055–2.034) compared with carriers of the G allele.ConclusionsThe single nucleotide polymorphism rs3732860 in the 3′‐untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.