Contribution of the IBD5 locus to Crohn's disease in the Swedish population.
OBJECTIVE
Recent data have controversially suggested that variants of the organic cation transport genes SLC22A4 (OCTN1) and SLC22A5 (OCTN2) are responsible for the contribution of IBD5 to disease susceptibility in Crohn's disease (CD). The objective of this study was to assess the contribution of the SLC22A4 variant (1672T) and SLC22A5 variant (-207C) together with three IBD5 haplotype markers in the previously uninvestigated Swedish CD population.


METHODS
The study comprised 178 CD patients and 143 healthy controls (HC). Genotyping for IBD5 single nucleotide polymorphisms (SNPs) IGR2096a_1, IGR2198a_1, IGR2230a_1, SLC22A4 1672T and SLC22A5 -207C was carried out using the TaqMan system. Associations with disease susceptibility and disease phenotype were investigated.


RESULTS
Strong linkage disequilibrium was observed between the investigated SNPs (D prime >0.92). IGR2096a_1 allelic frequency and homozygosity rates were associated with CD (44% CD versus 33.8% HC, p=0.008, OR=1.55 and 20% CD versus 12% HC, p=0.04, OR=1.93, respectively). Variant allelic frequency of SLC22A4, 1672T (44% versus 36%, p=0.03, OR=1.4) and homozygosity for the SLC22A4, SLC22A5 TC haplotype (1672T, -207C) (21.3% versus 12%, p=0.03, OR=1.78, population attributable risk (PAR)=11%) were associated with CD. There was no association between the allelic frequency of SLC22A5 and CD (46.6% CD versus 41.5% HC, p=0.82). The association of the TC haplotype with CD was not independent of the SNPs representing the extended IBD5 linkage interval.


CONCLUSIONS
The IBD5 locus is associated with CD in the Swedish population. The strongest association is with the marker SNP IGR2096a_1, lying p-telomeric to SLC22A4 and SLC22A5. The effect of the TC haplotype was not an independent determinant in this population.
Törkvist
Leif
L
Department of Medical & Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
Noble
Colin L
CL
Lördal
Mikael
M
Sjöqvist
Urban
U
Lindforss
Ulrik
U
Nimmo
Elaine R
ER
Löfberg
Robert
R
Russell
Richard K
RK
Satsangi
Jack
J
D000328:Adult; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D012307:Risk Factors; D000074058:Solute Carrier Family 22 Member 5; D013548:Sweden / Q000453:epidemiology; D027981:Symporters
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters