Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus

Blakemore, A. I. F.; Cox, Angela; González, Ana-Maria; Maskill, J. K.; Hughes, Marianne E.; Wilson, Robin; Ward, John D.; Duff, Gordon W.

doi:10.1007/s004390050055

Cited by 55 publications

(75 citation statements)

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“…It would be interesting to know the association of IL1RN*2 with CAD in the subgroups of diabetic individuals in these studies. In addition to the association reported here with an increased prevalence of CAD, the presence of allele 2 of the IL-1ra gene VNTR has been described as a risk factor for diabetic nephropathy (3). Therefore, the IL1RN VNTR genotype may provide a useful genetic marker for risk estimation of patients with type 2 diabetes.…”

supporting

confidence: 52%

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

et al. 2002

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Recently, inflammation has received considerable attention in the pathogenesis of both type 2 diabetes and atherosclerosis. The interleukin-1 receptor antagonist (IL-1ra) is a major modulator of the interleukin-1 proinflammatory pathway. We studied the relationship between a variable number tandem repeat (VNTR) polymorphism in intron 2 of the IL-1ra gene (IL1RN) and coronary artery disease (CAD) in patients with and without type 2 diabetes, following 787 consecutive patients admitted for suspected CAD. According to the current criteria of the American Diabetes Association, 250 patients had type 2 diabetes. In this group of patients, allele 2 carriers (n ‫؍‬ 108) had an increased prevalence of CAD compared with noncarriers (85.2 vs. 73.2%), a difference that remained significant in a multivariate logistic regression model (odds ratio 2.2, 95% CI 1.1-4.3, P ‫؍‬ 0.02). No association of CAD with allele 2 carrier status was present among nondiabetic patients (n ‫؍‬ 537). Enzyme-linked immunosorbent assays showed decreased baseline plasma levels of IL-1ra in patients with type 2 diabetes, which may in part explain the role of the IL1RN VNTR in these patients. Diabetes 51: [3582][3583][3584][3585] 2002

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supporting

confidence: 52%

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

et al. 2002

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“…in ulcerative colitis [3], multiple sclerosis [4], diabetic nephropathy [5] and alopecia areata [6]. The pathophysical background of this association is unknown and, as IL-1RA allele 2 is associated with increased IL-1RA protein production both in vitro [7] and in vivo (our unpublished observations), this association seems illogical.…”

Section: Genetic Regulation Of Il-1b Production 197mentioning

confidence: 79%

Presence of the IL‐1RA Allele 2 (IL1RN2) is Associated with Enhanced IL‐1β Production In Vitro*

1998

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Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA Allele 2 (IL1RN*2) is Associated with Enhanced IL-1b Production In Vitro. Scand J Immunol 1998;47:195-198 The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1a, IL-1b and the IL-1 receptor antagonist (IL-1RA). Each of these genes is polymorphic and there is increasing evidence that certain alleles are associated with increased susceptibility to a given disease of inflammatory nature. In the IL-1b gene there are two base-exchange polymorphisms in positions ¹511 and þ3953, and IL-1RA gene has a penta-allelic polymorphic site in intron 2 containing variable numbers of an 86-bp tandem repeat sequence. As the IL-1b/ IL-1RA ratio may be critical in the regulation of inflammation, we examined whether there are allelic associations between these loci (thus suggesting co-ordinate regulation) and whether these have an effect on the in vitro production of IL-1b. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL-1b gene (position ¹511) and with the absence of allele 2 of the IL-1b gene (position þ3953). Mononuclear cells from carriers of allele 2 (position ¹511) and non-carriers of allele 2 (position þ3953) had a slight, but non-significant, elevated capacity to produce IL-1b in vitro. However, IL-1RA allele 2 strongly increased in vitro production of IL-1b, regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL-1b gene are not major regulators of the in vitro IL-1b production, but the IL-1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.

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“…Allele 2 of the IL1RN VNTR has been associated with type 1 diabetes mellitus, lichen sclerosus, psoriasis, ulcerative colitis, systemic lupus erythematosus, diabetic nephropathy, multiple sclerosis, osteoporotic fractures, essential hypertension, attention deficit hyperactivity disorder, and alopecia areata, as well as survival following severe sepsis (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Polymorphisms within IL1B…”

Section: Maksymowych Et Almentioning

confidence: 99%

Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: An analysis of three Canadian populations

Maksymowych

Rahman

Reeve

et al. 2006

Arthritis & Rheumatism

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Objective. To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts.Methods. We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus.Results. A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P ‫؍‬ 0.0009 in the Alberta cohort, P ‫؍‬ 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P ‫؍‬ 0.0005 in the Alberta cohort, P ‫؍‬ 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/ rs3917356/rs3917354 (P ‫؍‬ 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations.Conclusion. These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS.

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Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus

Cited by 55 publications

References 0 publications

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Presence of the IL‐1RA Allele 2 (IL1RN2) is Associated with Enhanced IL‐1β Production In Vitro*

Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: An analysis of three Canadian populations

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Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus

Cited by 55 publications

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Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Presence of the IL‐1RA Allele 2 (IL1RN*2) is Associated with Enhanced IL‐1β Production In Vitro

Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: An analysis of three Canadian populations

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Presence of the IL‐1RA Allele 2 (IL1RN2) is Associated with Enhanced IL‐1β Production In Vitro*