A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis

McGarry, F; Neilly, J. B.; Anderson, Nicole; Sturrock, R D; Field, Matt

doi:10.1093/rheumatology/40.12.1359

Cited by 93 publications

(56 citation statements)

References 25 publications

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“…No associations with disease were observed, as compared with previous Scottish and Dutch studies (9,10). These discrepancies could reflect associations with distinct haplotypes in different populations.…”

Section: Discussioncontrasting

confidence: 87%

“…Other possibilities include genuine locus or allele heterogeneity among different populations and differences in risk-allele frequencies among studies (46)(47)(48). Substantial differences in IL1RN VNTR frequencies have been reported among different ethnic groups (9,10,25,41,49). Samples of similar size may have very different power to detect associations, depending on the frequency of the risk allele.…”

Section: Discussionmentioning

confidence: 99%

“…Two case-control studies from Scotland and The Netherlands have shown a disease association with allele 2 of a variable-number tandem repeat (VNTR) in intron 2 of the IL1RN gene (9,10). This same allele has been associated with insulin-dependent diabetes mellitus, lichen sclerosus, psoriasis, ulcerative colitis, systemic lupus erythematosus, diabetic nephropathy, multiple sclerosis, essential hypertension, attention deficit hyperactivity disorder, and alopecia areata, as well as survival following severe sepsis (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

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confidence: 99%

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High‐throughput single‐nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix‐assisted laser desorption ionization‐time‐of‐flight mass spectrometry

Maksymowych¹,

Reeve²,

Reveille³

et al. 2003

Arthritis & Rheumatism

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Objective. To examine single-nucleotide polymorphisms (SNPs) in the 3 region of the IL1RN gene in a large Caucasoid case-control series and in ankylosing spondylitis (AS) families from Western Canada by use of high-throughput MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry SNP typing.Methods. An association analysis was performed in a case-control cohort of 394 AS cases and 500 controls. Family-based association analysis was performed in 58 simplex and 13 multiplex families. Three SNPs located in the 3 region of the IL1RN gene (T/C at position 27810 in exon 4, T/C at position 30735 in exon 6, and G/C at position 31017 in exon 6) were examined by high-throughput MassArray MALDI-TOF mass spectrometry. Haplotype inference software programs were used to infer the most likely haplotypes and to compare haplotype frequencies, which were then further analyzed in family-based association studies by transmission disequilibrium tests.Results. The frequency of allele C at SNP position 30735 in exon 6 was significantly increased in AS cases (35.1%) versus controls (27.8%), as was the phenotype frequency (61.7% versus 48.6%). A significantly increased frequency of SNP allele G at position 31017 in exon 6 in cases (32.9%) versus controls (28.3%) was also noted. A highly significant difference in the overall distribution of haplotype frequencies was evident between cases and controls, with significant increases in the frequencies of the 27810C/30735C/31017C and 27810C/30735T/31017G haplotypes, but a significant reduction in the estimated frequency of the 27810C/ 30735T/31017C haplotype, in the AS cases. Estimation of haplotype frequencies based on 2 SNP markers indicated a highly significant increase in the 30735C/ 31017C haplotype and a highly significant decrease in the 30735T/31017C haplotype in cases compared with controls. Preliminary evidence for reduced transmission of the 27810C/30735T/31017C 3-marker haplotype was also found in family-based association analyses. Conclusion. Our data establish a highly significant disease association with markers in the IL1RN gene. In the absence of nonsynonymous coding sequence substitutions, it is possible that the primary diseaseassociated locus regulates gene expression. Association with specific haplotypes raises the possibility that the primary disease locus is in linkage disequilibrium with a specific combination(s) of markers in the IL1RN gene.Genetic modeling studies in twins have suggested that 97% of the population variance for developing ankylosing spondylitis (AS) can be explained by additive genetic effects, while comparison of disease concordance in identical twins (75%) versus HLA-B27-concordant dizygotic twins (27%) points to an important Dr. Maksymowych is a Senior Scholar with the Alberta

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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High‐throughput single‐nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix‐assisted laser desorption ionization‐time‐of‐flight mass spectrometry

Maksymowych¹,

Reeve²,

Reveille³

et al. 2003

Arthritis & Rheumatism

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“…With their prominent roles in the acute phase response, variants of these genes, the IL1 receptor type 1 and the receptor antagonist molecule might be associated with autoimmune and infectious disease susceptibility, and this is indeed the case for conditions such as septic shock, 28,29 ankylosing spondylitis, 27 juvenile rheumatoid arthritis 20 and myasthenia gravis. 17 Malaria pathogenesis might also be expected to be affected by variation in these genes for the same reason.…”

Section: Discussionmentioning

confidence: 99%

“…IL1B À511 C to T has been associated with gastric cancer, 21 Parkinson's disease, 22 asthma, 23 increased risk of febrile seizures 24 and inflammatory bowel disease, 25 while IL1B þ 3953 C to T has been associated with periodontitis 26 and inflammatory bowel disease. 25 An 86 bp repeat in the IL1RN gene has also been associated with a number of clinical conditions, including ankylosing spondylitis, 27 susceptibility to sepsis, 28,29 increased risk of death due to sepsis, 30 increased risk of febrile seizures 31 and susceptibility to tuberculosis. 32 One of the major factors contributing to mortality due to malaria infection is cerebral complications.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case–control study

et al. 2003

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Interleukin-1 (IL1) is a potent endogenous pyrogen and inducer of the acute phase response, and these innate immune responses are an important part of the human host's initial reaction to infection by the malaria parasite. In addition, several single-nucleotide polymorphisms (SNPs) in this region have previously been demonstrated to be associated with susceptibility to infectious disease. Therefore, a possible association with malaria susceptibility was investigated. A total of 13 polymorphic markers were used in a two-stage screening strategy to genotype a Gambian case -control study group by either restriction endonuclease digestion or the Sequenom MassARRAYt assay. This involved an initial screen of 188 severe cases and 188 mild controls, and if there was a significant association with a malaria phenotype (Po0.05); this was followed by screening of the remaining 1044 samples. Two markers showed significant association with malaria: interleukin-1 alpha þ 4845 G-T (P ¼ 0.035 for mild malaria versus controls) and interleukin-1 beta þ 3953 C-T (P ¼ 0.030 for mild malaria versus severe malaria). Haplotypes constructed using the SNPHAP programme were not associated with any of the malaria phenotypes investigated. In summary, if IL1 variants are involved in malaria susceptibility in the Gambia at all, then the effects are small.

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Lack of linkage of IL1RN genotypes with ankylosing spondylitis susceptibility

Jin

Zhang

Akey

et al. 2004

Arthritis & Rheumatism

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Photosensitivity is the leading symptom of cutaneous and systemic lupus erythematosus (LE). The role of sunlight in the induction of LE lesions has long been recognized, based on the observation that lesions are predominantly localized to sun-exposed areas of the body, especially the face, but also the head and neck area. Moreover, LE worsens during the summer period or in the weeks following increased sun exposure (1,2). Definite proof for a causative role of ultraviolet (UV) irradiation in the induction of LE came from experimental photoprovocation testing in the early 1990s (3). Those studies unraveled the fact that the UV action spectrum that provokes LE in sensitive individuals includes both the ultraviolet B (UVB; 290-320 nm) and the UVA (320-400 nm) range. Moreover, the studies showed that LE does not develop immediately after UV exposure, but after a delay of 2-3 weeks.In view of the central role of sunlight in provoking LE, it is important for patients to establish efficient UV protection throughout the year. This is a particular challenge for areas of the skin that cannot effectively be covered by clothing. Over

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A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis

Abstract: This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.

Cited by 93 publications

References 25 publications

High‐throughput single‐nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix‐assisted laser desorption ionization‐time‐of‐flight mass spectrometry

High‐throughput single‐nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix‐assisted laser desorption ionization‐time‐of‐flight mass spectrometry

Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case–control study

Lack of linkage of IL1RN genotypes with ankylosing spondylitis susceptibility

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