Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

C Enevold; Lasse Kjaer; Claus Henrik Nielsen; A Voss; Rasmus Sleimann Jacobsen; Marie-Louise From Hermansen; L Redder; A B Oturai; Peer Eske Jensen; K Bendtzen; Søren Jacobsen

doi:10.1007/s00296-014-3012-4

Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

C Enevold, Lasse Kjaer, Claus Henrik Nielsen, A Voss, Rasmus Sleimann Jacobsen, Marie-Louise From Hermansen, L Redder, A B Oturai, Peer Eske Jensen, K Bendtzen, Søren Jacobsen

Department of Clinical Medicine

17 Citations (Scopus)

Abstract

This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.

Original language	English
Journal	Rheumatology International
Volume	34
Issue number	10
Pages (from-to)	1401-1408
Number of pages	8
ISSN	0172-8172
DOIs	https://doi.org/10.1007/s00296-014-3012-4
Publication status	Published - 24 Sept 2014

Access to Document

10.1007/s00296-014-3012-4

Cite this

Enevold, C., Kjaer, L., Nielsen, C. H., Voss, A., Jacobsen, R. S., Hermansen, M-L. F., Redder, L., Oturai, A. B., Jensen, P. E., Bendtzen, K., & Jacobsen, S. (2014). Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes. Rheumatology International, 34(10), 1401-1408. https://doi.org/10.1007/s00296-014-3012-4

Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes. / Enevold, C; Kjaer, Lasse; Nielsen, Claus Henrik et al.

In: Rheumatology International, Vol. 34, No. 10, 24.09.2014, p. 1401-1408.

Research output: Contribution to journal › Journal article › Research › peer-review

Enevold, C, Kjaer, L, Nielsen, CH, Voss, A, Jacobsen, RS, Hermansen, M-LF, Redder, L, Oturai, AB, Jensen, PE, Bendtzen, K & Jacobsen, S 2014, 'Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes', Rheumatology International, vol. 34, no. 10, pp. 1401-1408. https://doi.org/10.1007/s00296-014-3012-4

@article{76b886fdee584342ac85331eafc0fcf3,

title = "Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes",

abstract = "This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.",

author = "C Enevold and Lasse Kjaer and Nielsen, {Claus Henrik} and A Voss and Jacobsen, {Rasmus Sleimann} and Hermansen, {Marie-Louise From} and L Redder and Oturai, {A B} and Jensen, {Peer Eske} and K Bendtzen and S{\o}ren Jacobsen",

year = "2014",

month = sep,

day = "24",

doi = "10.1007/s00296-014-3012-4",

language = "English",

volume = "34",

pages = "1401--1408",

journal = "Rheumatology International",

issn = "0172-8172",

publisher = "Springer",

number = "10",

}

TY - JOUR

T1 - Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

AU - Enevold, C

AU - Kjaer, Lasse

AU - Nielsen, Claus Henrik

AU - Voss, A

AU - Jacobsen, Rasmus Sleimann

AU - Hermansen, Marie-Louise From

AU - Redder, L

AU - Oturai, A B

AU - Jensen, Peer Eske

AU - Bendtzen, K

AU - Jacobsen, Søren

PY - 2014/9/24

Y1 - 2014/9/24

N2 - This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.

AB - This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.

U2 - 10.1007/s00296-014-3012-4

DO - 10.1007/s00296-014-3012-4

M3 - Journal article

C2 - 24719229

SN - 0172-8172

VL - 34

SP - 1401

EP - 1408

JO - Rheumatology International

JF - Rheumatology International

IS - 10

ER -

Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

Abstract

Access to Document

Fingerprint

Cite this