Relation between gene polymorphisms and the expression in colonic tissues of solute-linked carrier family 26 member A3 and Crohn's disease
10.3760/cma.j.issn.0254-1432.2017.10.008
- VernacularTitle:溶质相关载体26A3基因多态性及其在结肠组织中的表达水平与克罗恩病的关系
- Author:
Xiaoxiao SHAO
1
;
Xuanping XIA
;
Shuguang CAO
;
Shenglong XIA
;
Guangrong LU
;
Jinwei ZHONG
;
Xiuqing LIN
;
Jie JIN
;
Ran DING
;
Yi JIANG
Author Information
1. 温州医科大学附属第二医院消化内科
- Keywords:
SLC26A3;
Crohn disease;
Genes;
Polymorphism;
Colonic tissue expression
- From:
Chinese Journal of Digestion
2017;37(10):684-691
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the relation between genetic polymorphisms and the expression in colonic tissues of solute-linked carrier family 26 member A3 (SLC26A3) and susceptibility of Crohn's disease (CD) in Han population of Zhejiang Province.Methods A total of 265 CD patients and 566 gender-and age-matched healthy individuals were enrolled.Alleles and genotypes of SLC26A3 (rs17154444,rs7810937,rs7785539,rs2108225,rs6951457) were examined by SNaPshot.The linkage disequilibrium (LD) and haplotype were also analyzed.Eight patients with colonic CD and eight genderand age-matched patients with benign colonic polyps (control group) were selected.The expression level of SLC26A3 protein in the colonic tissue was detected by immunohistochemistry.T test and rank-sum test were performed for statistical analysis.Unconditional Logistic regression analysis was used to analyze the distributions of SLC26A3 polymorphisms and their effects on the clinicopathological features of CD patients.Results The frequencies of mutant allele of rs2108225,rs7785539 and rs6951457 of the CD group were 53.77% (285/530),4.72% (25/530) and 2.83% (15/530),and the frequencies of mutant genotype were 76.23 % (202/265),9.43 % (25/265) and 5.66 % (15/265),which were lower than those of the control group (60.95%,690/1 132;8.13%,92/1 132;6.10%,69/1 132;83.92%,475/566;15.37%,87/566 and 11.84%,67/566),and the differences were statistically significant (all P<0.05).The frequencies of mutant allele of rs17154444 and rs7810937 of the CD group were 10.19% (54/530) and 34.91 % (185/530),and the frequencies of mutant genotype were 18.49 % (49/265) and 56.23 % (149/ 265),compared with those of the control group (8.30%,94/1 132;30.92%,350/1 132;15.55%,88/566 and 51.77%,293/566),the differences were not statistically significant (all P>0.05).The frequency of mutant allele G of rs2108225 in patients with ileal CD was 47.89 % (91/190),and the frequency of mutant genotypeAG+GG was 65.26%(62/95),which were both lower than those of colonic CD (61.62%,122/198 and 85.86%,85/99),and the differences were statistically significant (both P<0.012 5).rs7810937,rs7785539 and rs2108225 were in a strong linkage disequilibrium.The frequencies of haplotypes AGG and ACA of the CD group were 53.96% (286/530) and 4.34% (23/530),which were lower than those of the control group (60.07%,680/1 132 and 7.51%,85/1 132),and the differences were statistically significant (52 =5.534,P=0.019;x2 =5.967,P=0.015).And the frequency of haplotype AGA of the CD group was 8.30% (44/530),which was higher than that of the control group (1.15%,13/1 132),and the difference was statistically significant (x2 =7.793,P<0.01).Furthermore,the expression level of SLC26A3 protein in colonic tissues of eight colonic CD patients was 0.19±0.07,which was lower than that of patients with benign colonic polyps (0.26 ±-0.03),and the difference was statistically significant (t=2.55,P=0.023).In addition,the expression levels of SLC26A3 protein in patients carrying genotype GG or AG of rs2108225 were 0.19±0.03 and 0.10±0.01,respectively,which were lower than that of patients carrying genotype AA (0.26± 0.02),and the differences were statistically significant (t=3.19,P=0.033;t=9.06,P=0.003).Conclusions The genetic polymorphismns and their haplotypes of SLC26A3 (rs7785539,rs2108225 and rs6951457) are associated with the susceptibility of CD,and SLC26A3 (rs2108225) polymorphism may affect the expression level of SLC26A3 protein in the colonic tissues.