SLC22A4 polymorphisms implicated in rheumatoid arthritis and Crohn's disease are not associated with rheumatoid arthritis in a Canadian Caucasian population.
OBJECTIVE
Single-nucleotide polymorphisms (SNPs) in the SLC22A4 gene encoding the organic cation transporter OCTN1 have been associated with rheumatoid arthritis (RA) in the Japanese population and with Crohn's disease in a Canadian cohort. The RA-associated and Crohn's disease-associated SNPs include, respectively, an intronic variant (slc2F2) and an exonic variant (1672T). We used a case-control approach to investigate the prevalence of these variants in a Canadian RA cohort and to determine whether RA and Crohn's disease share SLC22A4 susceptibility alleles.


METHODS
Nine hundred eighteen unrelated patients with RA, 507 patients with Crohn's disease, and 623 healthy controls were genotyped for the putatively RA-associated slc2F1 and slc2F2 variants and the Crohn's disease-associated SLC22A4 1672T variant.


RESULTS
Neither slc2F1 nor slc2F2 showed evidence for association with RA, the allele frequencies of these variants being significantly different in the Canadian population compared with those reported in the Japanese population, but not significantly different between patients with RA and controls. In addition, associations between the 1672T Crohn's disease risk allele and RA or between the slc2F1-A and slc2F2-T risk alleles and Crohn's disease were not detected in this study cohort, and the latter 2 alleles were not in linkage disequilibrium with the 1672T variant.


CONCLUSIONS
These observations do not support roles for any of the previously identified SLC22A4 disease risk alleles in RA susceptibility in the Canadian population. The slc2F1/slc2F2 risk alleles were not associated with Crohn's disease nor in linkage disequilibrium with the Crohn's disease-associated 1672T variant, and accordingly, also appear to be irrelevant to Crohn's disease susceptibility in the population under study.
Newman
Bill
B
University of Toronto and Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.
Wintle
Richard F
RF
van Oene
Mark
M
Yazdanpanah
Mehrdad
M
Owen
Julie
J
Johnson
Ben
B
Gu
Xiangjun
X
Amos
Christopher I
CI
Keystone
Edward
E
Rubin
Laurence A
LA
Siminovitch
Katherine A
KA
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002170:Canada; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D027701:Organic Cation Transport Proteins; D020641:Polymorphism, Single Nucleotide; D027981:Symporters; D044465:White People / Q000235:genetics
D026901:Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters