We validated these candidate genes in Japanese patients with CD and found a weak but possible association with both SLC22A4 (P=0.028) and DLG5 (P=0.023).
Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE.
Association with 11 SNPs spanning the SLC22A4 and SLC22A5 genes, including a putative RA-causing functional polymorphism (rs3792876 [slc2f2]) and a functional haplotype previously associated with CD, was investigated in 909 RA cases and 594 population controls in the UK.
Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.
Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus.
Previously, we identified 2 functionally relevant polymorphisms in the SLC22A4 / 22A5 genes at the IBD5 locus that alter gene/protein function and comprise a 2-allele haplotype ( SLC22A -TC) associated with increased risk for Crohn's disease (CD).
The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls.
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.
The article discusses current information on the relation between CARD15 variants and Crohn disease and the discoveries of SLC22A4/SLC22A5 and DLG5 gene variants that also confer risk for inflammatory bowel disease.
A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility.
There was a significant difference in the allele frequency (0.444 vs 0.519; P = 0.041) of the 1672T polymorphism in the SLC22A4 gene between controls and patients with CD.
The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians.
A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096.
Case-control analysis of the SLC22A4 1672T, SLC22A5-207C diplotype showed significant association (p=0.04) with CD susceptibility compared with controls.
L503F in SLC22A4 was the only nonsynonymous SNP significantly associated with CD (P=0.003), but was not associated with disease in the absence of other markers of the 250 kb risk haplotype.
Two variants, 1672C>T in SLC22A4 and -207G>C in SLC22A5, were shown to alter these genes' functions and were identified as genetic susceptibility factors for Crohn's disease (CD).
The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.