Prevalence of SLC22A4 1672T and SLC22A5 −207C combination defined TC haplotype in Hungarian ulcerative colitis patients

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. The aim of this study was to verify the prevalence rate of the haplotype called TC, determined by combination of two functional alleles of OCTN cation transporter genes (SLC22A4 1672T and SLC22A5 -207C combination variants) in ulcerative colitis patients and unrelated healthy controls. The "TC haplotype" has recently been suggested to confer risk for UC. A total of 121 unrelated Hungarian subjects with UC and 110 matched controls were genotyped for the two single nucleotide polymorphisms. The genotypes were determined by using PCR/RFLP assay and direct sequencing. The SLC22A4 1672T allele frequency was 46.7% in the patients with UC and 46.4% in the controls, whereas the SLC22A5 -207C allele occurred in 48.8% of the patients and 51.4% of the controls. The prevalence of the TC haplotype was 19% in the patient group and 22.7% in controls. Since there was no accumulation of the TC haplotype in the patient group, our observation suggests that carrying the TC haplotype is not associated with a higher risk for UC in the Hungarian population.

Plasma carnitine ester profiles in Crohn's disease and ulcerative colitis patients with different IGR2230a_1 genotypes

“…The TC haplotype of the slc22a4 and slc22a5 genes (Peltekova et al ., 2004) has been repeatedly shown to be associated with CD, although conflicting results have also been reported, possibly due to ethnographic reasons (Bene et al ., 2006b; Tosa et al ., 2006). In different populations UC either was (Palmieri et al ., 2006; Waller et al ., 2006) or was not associated (Peltekova et al ., 2004; Tosa et al ., 2006; Magyari et al ., 2007) with these slc22a gene variants. Furthermore, it was also demonstrated that this association can be dependent on other polymorphisms (IGR2096, IGR2198 and IGR2230) establishing an extended background risk haplotype (Noble et al ., 2005; Torkvist et al ., 2007).…”

“…CD and UC are complex diseases, and fine association mapping and functional dissection of the IBD5 region has yielded inconsistent results (Silverberg, 2006), showing that ethnic or geographical variations do occur. Previously we reported also that the TC haplotype of the slc genes does not represent a susceptibility factor for IBD in the Hungarian population (Bene et al ., 2006b; Magyari et al ., 2007). This view can be further complicated by the clinical heterogeneity of Crohn's disease and ulcerative colitis that may partly be accounted for by shared elements of genetic susceptibility, and can lead to misspecification of the disease type, especially with colonic involvement.…”

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

“…The L503F variant of SLC22A4 is more frequent in white persons from New Zealand who have Crohn's disease (Leung et al, 2006) (Table 18). Moreover, the L503F variant of SLC22A4 and the Ϫ207GϽC variant of SLC22A5 are found in adult Greek, British, and German patients with Crohn's disease, but not Italian or Hungarian patients (Gazouli et al, 2005;Török et al, 2005;Ferraris et al, 2006;Waller et al, 2006;Magyari et al, 2007;Taubert et al, 2009). Likewise, the genotype and haplotype frequencies of both of these variants are also increased in patients with ulcerative colitis .…”

Identifying Potential Drug Targets for the Treatment of Ulcerative Colitis Using Mendelian Randomization Combined with Co-localization Analysis

“…[37][38][39] The organic cation transporters OCTN1 and OCTN2, encoded by the SLC22A4 and SLC22A5 genes respectively, play key roles in regulating intestinal epithelial permeability and mucosal immune homeostasis. 40,41 Genetic variants in these genes have been implicated as ulcerative colitis risk factors, particularly the IBD5 risk haplotype. 41 Our MR analysis suggests that genetically-decreased expression of SLC22A5 is causally associated with higher ulcerative colitis susceptibility, likely due to impairment of epithelial barrier function and dysregulated mucosal immunity.…”