<i>HO‐1</i> promoter polymorphism associated with rheumatoid arthritis

Rueda, Blanca; Oliver, Javier; Robledo, Gema; López–Nevot, Miguel A.; Balsa, Alejandro; Pascual‐Salcedo, Dora; González-Gay, Miguel Á.; González‐Escribano, María Francisca; Martı́n, Javier

doi:10.1002/art.23048

Cited by 69 publications

(69 citation statements)

References 24 publications

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“…Allele and genotype frequencies were similar to those previously described. 31 No significant association between the genotypes or the individual allele frequencies, and the development of inhibitors was observed, in agreement with a recently published genome-wide association study by Astermark et al 32 (Online Supplementary Table S1; P>0.05).…”

Section: Single Nucleotide Polymorphismssupporting

confidence: 89%

“…Thus, HO-1 (GT) n microsatellite was identified as a genetic marker involved in rheumatoid arthritis. 31 The role of HO-1 in the anti-FVIII immune response was recently investigated in FVIII-deficient mice. 21 The induction of HO-1 by heme, or the administration of the catabolic heme products (CO, biluribin), drastically reduced the intensity of the anti-FVIII immune response.…”

Section: Discussionmentioning

confidence: 99%

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Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

et al. 2013

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Induction of heme oxygenase-1, a stress-inducible enzyme with anti-inflammatory activity, reduces the immunogenicity of therapeutic factor VIII in experimental hemophilia A. In humans, heme oxygenase-1 expression is modulated by polymorphisms in the promoter of the heme oxygenase-1-encoding gene (HMOX1). We investigated the relationship between polymorphisms in the HMOX1 promoter and factor VIII inhibitor development in severe hemophilia A. We performed a case-control study on 99 inhibitor-positive patients and 263 patients who did not develop inhibitors within the first 150 cumulative days of exposure to therapeutic factor VIII. Direct sequencing and DNA fragment analysis were used to study (GT) n polymorphism and single nucleotide polymorphisms located at -1135 and -413 in the promoter of HMOX1. We assessed associations between the individual allele frequencies or genotypes, and inhibitor development. Our results demonstrate that inhibitor-positive patients had a higher frequency of alleles with large (GT) n repeats (L: n≥30), which are associated with lesser heme oxygenase-1 expression (odds ratio 2.31; 95% confidence interval 1. 46-3.66; P<0.001]. Six genotypes (L/L, L/M, L/S, M/M, M/S and S/S) of (GT) n repeats were identified (S: n<21; M: 21≤n<30). The genotype group including L alleles (L/L, L/M and L/S) was statistically more frequent among inhibitor-positive than inhibitor-negative patients, as compared to the other genotypes (33.3% versus 17.1%) (odds ratio 2.21, 95% confidence interval 1.30-3.76; P<0.01). To our knowledge, this is the first association identified between HMOX1 promoter polymorphism and development of anti-drug antibodies. Our study paves the way towards modulation of the endogenous anti-inflammatory machinery of hemophilia patients to reduce the risk of inhibitor development Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

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Section: Single Nucleotide Polymorphismssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

et al. 2013

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“…As a result, Zconformation in (GT)n repeats on the human HO-1 gene promoter is identified as a basis for distinct transcriptional activities of HO-1 promoter with diverse (GT)n repeats. All those changes of conformations could possibly interfere some important regulation elements in HO-1 promoter, such as combination sites for NF-κB, so that influence the activity of HO-1 promoter [22,26].…”

Section: Discussionmentioning

confidence: 99%

“…The distribution of the numbers of (GT)n repeats was bimodal, with two main peak located at 23 and 30 GT repeats. Therefore, we divided the alleles into two subclasses, as previously reported [21][22][23][24][25]: class S (<25 repeats) and class L (≥ 25).…”

Section: Methodsmentioning

confidence: 99%

Polymorphism in heme oxygenase-1 (HO-1) promoter and alcohol are related to the risk of esophageal squamous cell carcinoma on Chinese males

Jl¹,

Zy²,

W³

et al. 2010

neo

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Chronic alcohol drinking is a strong risk factor for esophageal squamous cell carcinoma (ESCC). In this study, the correlation between the HO-1 gene promoter polymorphism and alcohol, along with the risk of ESCC on Chinese males, was analyzed.The case-control study was performed in 143 ESCC patients and 264 cancer-free controls. All subjects were males. Allelotypic frequencies of (GT)n repeat were examed by PCR-based genotyping and DNA sequencing. The frequencies of Lallele and L-allele carriers (S/L and L/L genotypes) was significantly higher in ESCC patients than in controls (p = 0.001 and 0.004), The adjusted ORs for ESCC with S/L and L/L genotypes vs S/S genotype was 2.212 (95% CI 1.297-3.775, p = 0.004). The adjusted ORs for light, moderate and heavy drinking was 1.467, 5.215 and 9.525 respectively among L-allele carriers (S/L and L/L genotypes ) and 1.389, 2.096 and 3.039 respectively for the S/S genotype. Length of a (GT)n repeat in the HO-1 gene promoter may be associated with the development of ESCC in Chinese male drinkers. Reducing alcohol intake might be most protective among L-allele carriers of this polymorphism.

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“…Association between HMOX1 polymorphisms and several disease conditions have been proposed, including chronic obstructive pulmonary disease, vascular restenosis, and rheumatoid arthritis (56)(57)(58)(59)(60). A recent study has described an association between HMOX1 promoter length polymorphisms and renal function after renal transplantation (61), though similar studies report no associations in the outcome of cardiac or renal transplantation (62,63).…”

Section: Heme Oxygenase-1: Gene Regulationmentioning

confidence: 99%

Heme Oxygenase-1/Carbon Monoxide

Ryter

Choi

2009

Am J Respir Cell Mol Biol

250

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Heme oxygenase-1 (HO-1), a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO activity cleaves heme to form biliverdin-IXa, carbon monoxide (CO), and iron. Genetic experiments have revealed a central role for HO-1 in tissue homeostasis, protection against oxidative stress, and in the pathogenesis of disease. Four decades of research have witnessed not only progress in elucidating the molecular mechanisms underlying the regulation and function of this illustrious enzyme, but also have opened remarkable translational applications for HO-1 and its reaction products. CO, once regarded as a metabolic waste, can act as an endogenous mediator of cellular signaling and vascular function. Exogenous application of CO by inhalation or pharmacologic delivery can confer cytoprotection in preclinical models of lung/vascular injury and disease, based on anti-apoptotic, antiinflammatory, and anti-proliferative properties. The bile pigments, biliverdin and bilirubin, end products of heme degradation, have also shown potential as therapeutics in vascular disease based on anti-inflammatory and anti-proliferative activities. Further translational and clinical trials research will unveil whether the HO-1 system or any of its reaction products can be successfully applied as molecular medicine in human disease.

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HO‐1 promoter polymorphism associated with rheumatoid arthritis

Cited by 69 publications

References 24 publications

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter

Polymorphism in heme oxygenase-1 (HO-1) promoter and alcohol are related to the risk of esophageal squamous cell carcinoma on Chinese males

Heme Oxygenase-1/Carbon Monoxide

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