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Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility.

Jönsen A, Bengtsson AA, Sturfelt G, Truedsson L - Arthritis Res. Ther. (2004)

Bottom Line: We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE.HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7-4.5).It also confirms earlier findings regarding the HLA DR3-DQ2-C4AQ0 haplotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Lund University Hospital, Lund, Sweden. andreas.jonsen@reum.lu.se

ABSTRACT
Dysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3, HLA DQ2, C4AQ0, Fcgamma receptor IIa (FcgammaRIIa) genotype R/R, Fcgamma receptor IIIa (FcRgammaIIIa) genotype F/F, mannan-binding lectin (MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype 2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7-4.5). Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after combination with FcgammaRIIa R/R, FcgammaRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcgammaRIIa R/R and IL-1Ra 2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5-95.4). This study demonstrates that certain combinations of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier findings regarding the HLA DR3-DQ2-C4AQ0 haplotype.

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Distribution of genetic variants studied in 143 patients with SLE and 200 healthy blood donors. DR3 represents the haplotype DR3-DQ2-C4AQ0. F, phenylalanine; H, histidine; Int, intermediate; MBL, mannan-binding lectin; R, arginine; V, valine.
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Figure 1: Distribution of genetic variants studied in 143 patients with SLE and 200 healthy blood donors. DR3 represents the haplotype DR3-DQ2-C4AQ0. F, phenylalanine; H, histidine; Int, intermediate; MBL, mannan-binding lectin; R, arginine; V, valine.

Mentions: A strong association between the HLA DR3-DQ2-C4AQ0 haplotype and SLE was found, although this haplotype also was common among the controls. HLA DR2 was present in 50 of the 143 SLE patients and 72 of the 200 controls, while DR4 frequencies were 45/143 and 72/200, respectively. In the SLE group, HLA DQ2 was present in 80 of 143 cases, while DQ3 and DQ6 was recorded in 60 of 143 and 85 of 143 cases, respectively. The corresponding numbers in the control group were for DQ2, 73/200; for DQ3, 100/200; and for DQ6, 112/200. Other DR and DQ variants were less common. Ninety percent of the SLE patients with HLA DR3 displayed the haplotype DR3-DQ2-C4AQ0, compared with 86% of the controls. The frequencies of the FcγRIIa, FcγRIIIa, MBL, and IL-1Ra genotypes are displayed in Fig. 1. The FcγRIIa R/R, FcγRIIIa F/F, IL-1Ra 2/2, and MBL-low genotypes were not individually associated with SLE.


Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility.

Jönsen A, Bengtsson AA, Sturfelt G, Truedsson L - Arthritis Res. Ther. (2004)

Distribution of genetic variants studied in 143 patients with SLE and 200 healthy blood donors. DR3 represents the haplotype DR3-DQ2-C4AQ0. F, phenylalanine; H, histidine; Int, intermediate; MBL, mannan-binding lectin; R, arginine; V, valine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064866&req=5

Figure 1: Distribution of genetic variants studied in 143 patients with SLE and 200 healthy blood donors. DR3 represents the haplotype DR3-DQ2-C4AQ0. F, phenylalanine; H, histidine; Int, intermediate; MBL, mannan-binding lectin; R, arginine; V, valine.
Mentions: A strong association between the HLA DR3-DQ2-C4AQ0 haplotype and SLE was found, although this haplotype also was common among the controls. HLA DR2 was present in 50 of the 143 SLE patients and 72 of the 200 controls, while DR4 frequencies were 45/143 and 72/200, respectively. In the SLE group, HLA DQ2 was present in 80 of 143 cases, while DQ3 and DQ6 was recorded in 60 of 143 and 85 of 143 cases, respectively. The corresponding numbers in the control group were for DQ2, 73/200; for DQ3, 100/200; and for DQ6, 112/200. Other DR and DQ variants were less common. Ninety percent of the SLE patients with HLA DR3 displayed the haplotype DR3-DQ2-C4AQ0, compared with 86% of the controls. The frequencies of the FcγRIIa, FcγRIIIa, MBL, and IL-1Ra genotypes are displayed in Fig. 1. The FcγRIIa R/R, FcγRIIIa F/F, IL-1Ra 2/2, and MBL-low genotypes were not individually associated with SLE.

Bottom Line: We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE.HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7-4.5).It also confirms earlier findings regarding the HLA DR3-DQ2-C4AQ0 haplotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Lund University Hospital, Lund, Sweden. andreas.jonsen@reum.lu.se

ABSTRACT
Dysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3, HLA DQ2, C4AQ0, Fcgamma receptor IIa (FcgammaRIIa) genotype R/R, Fcgamma receptor IIIa (FcRgammaIIIa) genotype F/F, mannan-binding lectin (MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype 2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7-4.5). Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after combination with FcgammaRIIa R/R, FcgammaRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcgammaRIIa R/R and IL-1Ra 2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5-95.4). This study demonstrates that certain combinations of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier findings regarding the HLA DR3-DQ2-C4AQ0 haplotype.

Show MeSH
Related in: MedlinePlus