TNFalpha and IL-10 Gene Polymorphisms in Inflammatory Bowel Disease. Association of -1082 AA Low Producer IL-10 Genotype with Steroid Dependency

Castro‐Santos, Patricia; Suárez, Ana; López-Rivas, Laureano; Mozo, Lourdes; Gutiérrez, Carmen

doi:10.1111/j.1572-0241.2006.00501.x

Cited by 52 publications

(32 citation statements)

References 51 publications

(54 reference statements)

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“…In subsequent studies, IL10 promoter polymorphisms were sporadically associated with IBD. For example, G-1082A SNPs was associated with UC and/or CD in Spanish, Australian, New Zealand, Italian, and Mexican studies (Fernandez et al 2005;Fowler et al 2005;Castro-Santos et al 2006;Hong et al 2008;Tedde et al 2008;Garza-Gonzalez et al 2010;Wang et al 2011), but the findings were not consistent, showing associations for both G and A allele (or genotypes containing those alleles). The polymorphism C-592A was also associated with CD in Canadian pediatric patients (Amre et al 2009).…”

Section: Discussionmentioning

confidence: 94%

The Polymorphism rs3024505 (C/T) Downstream of the <i>IL10 </i>Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

Mijač

Petrović

Djuranović

et al. 2016

Tohoku J. Exp. Med.

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Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/ T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

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Section: Discussionmentioning

confidence: 94%

The Polymorphism rs3024505 (C/T) Downstream of the <i>IL10 </i>Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

Mijač

Petrović

Djuranović

et al. 2016

Tohoku J. Exp. Med.

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“…On the other hand, IL-10-1082 G/A polymorphism has been reported to influence susceptibility to UC [38,86,126]. A gender effect has been reported, with women of AG/AA genotypes of IL-10-1082 G/A, having a higher risk of developing UC at a younger age and is related to the lower IL-10 production associated with the -1082A allele and to the IL10 downregulating effect of estrogens [86].…”

Section: Discussionmentioning

confidence: 98%

“…Although the frequency of allele G was reported to be slightly higher in Iranian Azeri Turkish IBD patients, it did not reach statistical significance [110]. Further, no association of TNF-α(-308G/A) polymorphism with IBD susceptibility was found in Australian [82], Brazilian [60,130], Canadian [100], Chinese [106,131], Czech [132], French [133], Indian [108], Korean [115], Newfoundland [27], Spanish [126], and Turkish [120] populations. The reason for these differences in the TNF-α genetic associations with IBD etiology might be the variations in sample size, genotyping methods, and/or ethnicity itself as frequencies of alleles and genotypes of TNF-α (-308G/A) also vary in different ethnic healthy populations worldwide [39] ( Table 3).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

Al-Robayan¹,

Arfin²,

Meghaiseeb³

et al. 2016

New Insights Into Inflammatory Bowel Disease

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“…Epidemiological studies and genome-wide linkage analyses have established the genetic predisposition to inflammatory bowel diseases, however, information is lacking with regard to the genes that are responsible (4). Therefore, the association between the polymorphism of various genes and UC has been previously studied (5)(6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

et al. 2014

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Abstract. Previous studies have demonstrated the protective role of inducible heat-shock protein (HSP) 70 in intestinal cells. The HSP70-2 gene has a PstI site due to an A-G transition at the 1,267 position and different genotypes are associated with various levels of mRNA expression. The present study aimed to clarify the effect of the HSP70-2 polymorphism on the risk of ulcerative colitis (UC), including its clinical phenotypes. A total of 121 patients with UC and 500 healthy control (HC) subjects participated in the study. To assess the polymorphisms at the 1,267 position of the HSP70-2 gene, restriction fragment length polymorphism analysis was performed. The subjects in the study were classified by disease behavior, severity and extent of disease. Although no significant difference of the HSP70-2 genotype distribution was identified between the HC and UC groups, the BB genotype exhibited a lower risk of the steroid-dependent phenotype [odds ratio (OR), 0.12; 95% confidence interval (CI), 0.02-0.95; P=0.02]. The same genotype was also associated with a lower risk of the refractory phenotype (OR, 0.16; 95% CI, 0.04-0.73; P= 0.01). There was no direct correlation between the polymorphism of the HSP70-2 gene and UC susceptibility. However, there was an association between a reduced risk of the steroid-dependent and refractory phenotypes of UC and the BB genotype. IntroductionUlcerative colitis (UC) is a condition that affects the colon and rectum and usually involves the innermost lining mucosa. The condition presents as continuous areas of inflammation, with no segments of normal mucosa (1). UC is characterized by chronic, relapsing colonic inflammation with an unknown etiology. Immune dysregulation and genetic factors are known to play important roles in the pathogenesis of UC.UC is a multifactorial, polygenic disease with possible genetic heterogeneity, and different genetic backgrounds may account for the numerous clinical patterns of UC (2,3). Epidemiological studies and genome-wide linkage analyses have established the genetic predisposition to inflammatory bowel diseases, however, information is lacking with regard to the genes that are responsible (4). Therefore, the association between the polymorphism of various genes and UC has been previously studied (5-11).Heat-shock proteins (HSPs), in particular the HSP70 family, play important roles in intracellular trafficking and conformation of proteins by acting as a molecular chaperone, thus involving them in immune regulation (12). Three members of the HSP gene, known as HSP70-1, -2 and-Hom, have been mapped to the class-III region of the human major histocompatibility complex (MHC); 92 kb telomeric of the complement C2 locus (13). HSP70-1 and -2 encode the same protein, known as inducible HSP70. A previous study showed the protective role of inducible HSP70 in intestinal cells (14). HSP70 was also detected in the inflamed colonic mucosa of Crohn's disease (CD) patients (15), and therefore, the HSP70 gene family has been suggested to be a possible candidat...

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TNFalpha and IL-10 Gene Polymorphisms in Inflammatory Bowel Disease. Association of -1082 AA Low Producer IL-10 Genotype with Steroid Dependency

Abstract: The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.

Cited by 52 publications

References 51 publications

The Polymorphism rs3024505 (C/T) Downstream of the <i>IL10 </i>Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

The Polymorphism rs3024505 (C/T) Downstream of the <i>IL10 </i>Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

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