The rs12532734 Polymorphism Near the Solute Carrier 26A3 Gene Locus Is Associated With Gallstone Disease in Children

Gallstones are increasingly frequent in children. In this candidate gene study, we genotyped 5 gene variants (ANO1, SPTLC3, TMEM147, TNRC6B, rs12532734) from a recent gallstone genome-wide association study (GWAS) in a cohort of 214 children with gallstones and 172 gallstone-free adult controls. In total, 138 genotyped children presented with symptomatic gallstone disease, 47 underwent cholecystectomy, and 126 received ursodeoxycholic acid (UDCA) as therapy for stones. Among 5 tested variants, the rs12532734 polymorphism modulated the gallstone risk in the studied cohort. Its genotype distribution significantly (P = 0.025) departed from the Hardy-Weinberg equilibrium among cases, and the common allele was associated with increased odds of developing gallstones at young age (OR = 1.69, P = 0.014). SLC26A3 is the nearest gene to rs12532734 and is involved in the transepithelial bicarbonate and chloride transport. The association of rs12532734 with pediatric gallstones is a novel finding warranting further investigations also with regard to biliary bicarbonate flux and bile composition.

[1]  F. Lammert,et al.  Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children , 2022, Liver international : official journal of the International Association for the Study of the Liver.

[2]  C. A. Shaw,et al.  Genome-wide Analysis Identifies Novel Gallstone-susceptibility Loci Including Genes Regulating Gastrointestinal Motility , 2021, medRxiv.

[3]  Qin Yu.  Slc26a3 (DRA) in the Gut: Expression, Function, Regulation, Role in Infectious Diarrhea and Inflammatory Bowel Disease. , 2020, Inflammatory bowel diseases.

[4]  T. Lehtimäki,et al.  Genetic polymorphism of sterol transporters in children with future gallstones. , 2018, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[5]  F. Lammert,et al.  Genetics of gallstone disease , 2018, European journal of clinical investigation.

[6]  Yi Jiang,et al.  Association of ulcerative colitis with solute-linked carrier family 26 member A3 gene polymorphisms and its expression in colonic tissues in Chinese patients , 2018, International Journal of Colorectal Disease.

[7]  U. Poddar.  Gallstone disease in children , 2010, Indian pediatrics.

[8]  Yusuke Nakamura,et al.  A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population , 2009, Nature Genetics.

[9]  Shmuel Muallem,et al.  The solute carrier 26 family of proteins in epithelial ion transport. , 2008, Physiology.

[10]  F. Lammert,et al.  Genetic and environmental influences on symptomatic gallstone disease: A Swedish study of 43,141 twin pairs , 2005, Hepatology.

[11]  J. Kere,et al.  SLC26A3 mutations in congenital chloride diarrhea , 2002, Human mutation.

[12]  J. Martí-Climent,et al.  Assessment of biliary bicarbonate secretion in humans by positron emission tomography. , 1999, Gastroenterology.

[13]  J. Kere,et al.  Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait. , 1998, American journal of human genetics.