In the Czech population we examined its genetic association using variants of the SLC22A4 (rs1050152), SLC22A5 (rs2631367), two single nucleotide polymorphisms (SNPs) shown to be associated with CD in genome-wide studies (rs6596075 and rs2188962), and four SNPs previously shown to tag the haplotype blocks 4, 7, 9, 10 of the IBD5 locus (IGR2063b_1, IGR2230a_1, IGR100Xa_1, IGR3236a_1).
Our aim was to assess the involvement on T1D and RA of IL4 polymorphisms considered individually and in combination with other polymorphisms in 5q31-33, specifically in the OCTN locus, where the L503F polymorphism has been associated with Crohn's disease and other Th1 diseases.
The human OCTN1 (SLC22A4) reconstituted in liposomes catalyzes acetylcholine transport which is defective in the mutant L503F associated to the Crohn's disease.
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.
CD was associated with NOD2 carrier (6.93% CD, 2.15% Controls, P = 0.007), ATG16L1 Thr300Ala (36.1% CD, 29.3% Controls, P = 0.003), SLC22A4 and SLC22A5 (IBD5 locus) functional SNPs (Leu503Phe [10.5% CD, 7.6% Controls, P = 0.05] and g-207c [41.3% CD, 35.7% Controls, P = 0.03], respectively), and IL23R rs2201841 (18.2% CD, 13.8% Controls, P = 0.03), but not IRGM variants, nor three African ancestral NOD2 nonsynonymous variants.IBD5 risk was recessive.
Case-control data on New Zealand Caucasians show no differences for CD risk between individuals carrying the L503F OCTN1 C-allele when compared with those carrying the variant T-allele.
Several studies have demonstrated that the organic cation/carnitine transporter 1 (<i>OCTN1</i>) non-synonymous variant L503F is associated with susceptibility to CD.
We found statistically significant association of polymorphisms rs1050152 in gene SLC22A4 (p = 0.005, OR = 2.177, 95% CI = 1.270-3.526) and rs2631372 in gene SLC22A5 (p = 0.001, OR = 0.473, 95% CI = 0.307-0.731) and TC haplotype of both polymorphisms (p = 0.006, OR = 1,541, 95% CI = 1.130-2.100) with refractory Crohn's disease (CD) in Slovenian patients who do not respond to standard therapy, including patients who develop fistulas.
Recently, two functional variants within the SLC22A4 and SLC22A5 genes at this locus (IBD5), L503F (c.1507C > T) and G-207C (c.-207G > C), have been proposed to contribute directly to susceptibility to CD.
To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects.
To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD.
Other studies have found that mutation of rs1143627 of IL1B (allelic model: OR 2.97; 95% CI 1.74-5.05, P < 0.001) and rs1050152 of OCTN1 (allelic model: OR 1.637, 95% CI 1.078-2.485, P = 0.021) increased the proportion of IBD-associated CRC in the population.
Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies.
We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.
The SLC22A4 polymorphisms slc2F1 (rs2073838) and slc2F2 (rs3792876) are reported to be associated with rheumatoid arthritis (RA) in Japanese, but the associations have not been replicated.
We found no evidence for an association between RA and either the SNP (rs3792876 [slc2f2]) or the haplotype previously reported to be associated with RA in a Japanese population.
For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron.
The SLC22A4 polymorphisms slc2F1 (rs2073838) and slc2F2 (rs3792876) are reported to be associated with rheumatoid arthritis (RA) in Japanese, but the associations have not been replicated.
Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies.