Background and aims:The OCTN1(SLC22A4 1672C→ T) and OCTN2(SLC22A5-207G→ C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease(CD) ,but their contribution in child...
详细信息
Background and aims:The OCTN1(SLC22A4 1672C→ T) and OCTN2(SLC22A5-207G→ C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease(CD) ,but their contribution in children has not been ***:These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms(SNPs) (IGR2096a-1,IGR2198a-1,and IGR2230a-1) were examined in 299 Scottish children(200 with CD,74 with ulcerative colitis(UC) ,and 25 with indeterminate colitis(IC) ) ,together with 502 parents(for transmission disequilibrium testing) and 250 ***:All SNPs were in strong linkage disequilibrium(D’ >0.94) .TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease(IBD) (p = 0.01) and CD(p = 0.04) .Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases(p < 0.04) .The homozygous mutant OCTN1/2 haplotype was increased in IBD(24.3% v 16.1%,p = 0.02) and UC(28.2% v 16.1%,p = 0.02) compared with *** OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease *** analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight,height,and BMI centile(< 9th centile) at diagnosis(weight:87.9% v 67.3%(p = 0.002) ,odds ratio(OR) = 3.52(95% confidence interval,1.51 to 8.22) ;height:84.1% v 68.4%(p< 0.05) ,OR = 2.44(1.00 to 5.99) ;BMI:79.6% v 61.1%(p = 0.02) ,OR = 2.49(1.14 to 5.44) ) ,and lower weight centile at follow up(87.5% v 64.6%(p = 0.03) ,OR = 3.83(1.03 to 14.24) ) .Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis(p = 0.02,OR = 3.41(1.20 to 9.66) ) .Conclusions:These data implicate variants within the IBD5 haplotype,as determinants of disease susceptibility and growth indices in early onset *** OCTN1/2 variants remain potential positional candidate genes,but require further analysis.
暂无评论