Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants
(2013) In Circulation: Cardiovascular Genetics 6(3). p.255-263- Abstract
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in... (More)
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3983160
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- lupus erythematosus, interferon regulatory factor-8, genes, disease, coronary, cardiovascular disease, carotid intima-media thickness, myocardial ischemia, systemic
- in
- Circulation: Cardiovascular Genetics
- volume
- 6
- issue
- 3
- pages
- 255 - 263
- publisher
- American Heart Association
- external identifiers
-
- wos:000320580700006
- scopus:84884498097
- pmid:23661672
- ISSN
- 1942-325X
- DOI
- 10.1161/CIRCGENETICS.113.000044
- language
- English
- LU publication?
- yes
- id
- 9a854f35-b7ba-4e87-bb95-70ac73298db4 (old id 3983160)
- date added to LUP
- 2016-04-01 09:51:46
- date last changed
- 2022-04-27 08:18:40
@article{9a854f35-b7ba-4e87-bb95-70ac73298db4, abstract = {{Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.}}, author = {{Leonard, Dag and Svenungsson, Elisabet and Sandling, Johanna K. and Berggren, Olof and Jönsen, Andreas and Bengtsson, Christine and Wang, Chuan and Jensen-Urstad, Kerstin and Granstam, Sven-Olof and Bengtsson, Anders and Gustafsson, Johanna T. and Gunnarsson, Iva and Rantapaa-Dahlqvist, Solbritt and Nordmark, Gunnel and Eloranta, Maija-Leena and Syvanen, Ann-Christine and Ronnblom, Lars}}, issn = {{1942-325X}}, keywords = {{lupus erythematosus; interferon regulatory factor-8; genes; disease; coronary; cardiovascular disease; carotid intima-media thickness; myocardial ischemia; systemic}}, language = {{eng}}, number = {{3}}, pages = {{255--263}}, publisher = {{American Heart Association}}, series = {{Circulation: Cardiovascular Genetics}}, title = {{Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants}}, url = {{http://dx.doi.org/10.1161/CIRCGENETICS.113.000044}}, doi = {{10.1161/CIRCGENETICS.113.000044}}, volume = {{6}}, year = {{2013}}, }