Human Genetics

, Volume 125, Issue 4, pp 381–391

Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2): novel haplotype block including six newly identified variants linked to reduced expression

  • Olga Renner
  • Simone Harsch
  • Elke Schaeffeler
  • Matthias Schwab
  • Dietmar M. Klass
  • Wolfgang Kratzer
  • Eduard F. Stange
Original Investigation

DOI: 10.1007/s00439-009-0630-0

Cite this article as:
Renner, O., Harsch, S., Schaeffeler, E. et al. Hum Genet (2009) 125: 381. doi:10.1007/s00439-009-0630-0

Abstract

The apical sodium-dependent bile acid transporter (SLC10A2) plays a key role in the reabsorption of luminal bile acids into the enterohepatic circulation. Rare variations in SLC10A2 have been reported to be associated with Crohn’s disease, primary bile acid malabsorption and familial hypertriglyceridemia; however, variants associated with reduced SLC10A2 expression have not been reported to date. In this study, we have performed a sequence analysis of SLC10A2 using genomic DNA of 93 individuals. A new haplotype structure was identified including ten variants with complete linkage disequilibrium (LD′ = 1.0, r2 = 1.0) of which six polymorphisms were novel. The sequence variants were confirmed in three independent cohorts (n = 1,290) by a recently established MALDI-TOF MS iPLEX™ assay. Remarkably, haplotype carriers with the minor allele exhibited significant reduced ileal SLC10A2 expression on mRNA levels (2.6-fold, P = 0.0009) and protein levels (2.4-fold, P = 0.0157). In future studies a single tag SNP selected of this haplotype block will provide reliable genetic testing to investigate systemically the influence of the SLC10A2 haplotype for disease susceptibility and/or drug response.

Supplementary material

439_2009_630_MOESM1_ESM.eps (59 kb)
Supplementary material (EPS 59 kb)
439_2009_630_MOESM2_ESM.eps (173 kb)
Influence of haplotype block on SLC10A2 mRNA and protein expression comparing individuals without haplotype block (n=74) to carriers of the haplotype (n=11). The expression analysis was performed in human ileal mucosal biopsies and is represented as scatter dot plot (a) and as well as box and whiskers (b). Quantitative analysis of SLC10A2 mRNA expression is given as transcript numbers. All data are represented as means ± SEM. A P value of <0.05 was considered statistically significant (EPS 172 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Olga Renner
    • 1
  • Simone Harsch
    • 1
  • Elke Schaeffeler
    • 1
  • Matthias Schwab
    • 1
  • Dietmar M. Klass
    • 2
  • Wolfgang Kratzer
    • 2
  • Eduard F. Stange
    • 3
  1. 1.Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of TübingenStuttgartGermany
  2. 2.Department of Medicine IUniversity Hospital of UlmUlmGermany
  3. 3.Department of Internal Medicine IRobert Bosch HospitalStuttgartGermany