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News

Common genetic variations for intrahepatic cholestasis of pregnancy

The most recent issue of the American Journal of Gastroenterology performs a comprehensive analysis of common genetic variation around 6 candidate loci for intrahepatic cholestasis of pregnancy.

News image

Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component.

Heterozygous mutations of canalicular transporters occur in a subset of intrahepatic cholestasis of pregnancy cases and a population susceptibility allele (p.444A) has been identified in ABCB11.

Dr Dixon and colleagues from the United Kingdom investigated common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19).

The team analyzed 563 intrahepatic cholestasis of pregnancy patients of white western European origin, and 642 controls in a case–control design.

Single-nucleotide polymorphism (SNP) markers were selected from the HapMap data set.

There is a key role for common variation around the ABCB4 and ABCB11 loci
American Journal of Gastroenterology

The team performed genotyping by allelic discrimination assay on a robotic platform.

Following quality control, SNP data were analyzed by Armitage's trend test.

Cochran–Armitage trend testing identified 6 SNPs in ABCB11 together with 6 SNPs in ABCB4 that showed significant evidence of association.

The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10−4 (rs3815676) and for ABCB4 it was 4.6×10−7(rs2109505).

The team performed conditional analysis of the 2 clusters of association signals that suggested a single signal in ABCB4 but evidence for 2 independent signals in ABCB11.

To confirm these findings, the team performed a second study in a further 227 cases, which confirmed and strengthened the original findings.

Dr Dixon's team concludes, "Our analysis of a large cohort of intrahepatic cholestasis of pregnancy cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of intrahepatic cholestasis of pregnancy susceptibility."

Am J Gastroenterol 2014; 109:76–84
27 January 2014

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