Association of variants of ABCB11 with transient neonatal cholestasis

摘要

Background The significance of ABCB11 variants have been studied in some cholestatic diseases, but this is not clear in transient neonatal cholestasis (TNC). The aim of the present study was to explore the association between ABCB11 variants and TNC. Methods This was a case-control study. A total of 192 children with TNC referred to a tertiary referral hospital in eastern China were enrolled as subjects, and 196 healthy children were selected as controls. Part of the promoter and exons of the ABCB11 gene were sequenced directly. The single nucleotide polymorphism (SNP) site of V444A was tested using fluorescent quantitative polymerase chain reaction. Potential consequences of variants were predicted using bioinformatics software. The biochemistry indices were compared between the patients with or without possibly pathogenic variants/mutations. Results Twenty-eight variants, including 14 novel ones, were detected. Four novel, possibly pathogenic mutations (I416I, K436N, R928Q and IVS7+5G>A) were detected in six subjects. The γ-glutamyltransferase level of these six was lower than in the others (P = 0.054). The genotype distribution of the four common SNP sites, V444A, A535A, A865V and A1082A, was not significantly different between TNC patients and controls. Conclusions Approximately 3% of TNC cases can be attributed to ABCB11 mutations. Pediatrics International