Association of rs17095355 Polymorphism and Extrahepatic Biliary Atresia among Filipinos

Fresthel Monica M. Climacosa,1 Germana Emerita V. Gregorio2 and Catherine Lynn T. Silao2,3

1College of Medicine, University of the Philippines Manila
2Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
3Institute of Human Genetics, National Institutes of Health,
University of the Philippines Manila

Background. Extrahepatic biliary atresia (EHBA) causes a rare obstructive cholestasis in infants. Kasai portoenterostomy if done before the third month of life may relieve obstruction. Genetic predisposition has been implicated in EHBA etiopathogenesis with rs17095355 polymorphism having the strongest association. We determined the association between rs17095355 and EHBA susceptibility of Filipino children, and described the outcome in each genotype among timely operated patients.

Methods. Thirty-four histologically diagnosed EHBA patients and thirty-three age- and sex-matched controls were recruited. Genomic DNA was extracted from peripheral blood and subjected to PCR and direct sequencing. Success of surgery among patients operated before 90 days of life was assessed by jaundice clearance six months post-surgery and native liver survival two and five years post-surgery.

Results. There was no significant difference among individuals carrying T and C alleles in developing EHBA (OR:1.36; 95%CI:0.65–2.86). Jaundice persisted post-operatively in 75%, 33% and 27% of Kasai-operated homozygous T (T/T), homozygous C (C/C) and heterozygous (C/T) patients, respectively. Fifty percent of Kasai-operated C/C and C/T patients retained their native liver whereas all Kasai-operated T/T patients required liver transplantation two years post-surgery.

Conclusion. There is insufficient evidence to associate rs17095355 in EHBA development among Filipinos. Further investigation is warranted to elucidate genetic mechanisms in EHBA etiopathogenesis.

Key Words: biliary atresia, single nucleotide polymorphism, hepatic portoenterostomy