MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus

N J McHugh, P Owen, B Cox, J Dunphy, K Welsh

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Abstract

Objective: To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE.

Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples.

Results: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303; DRB1*0701/2; TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)).

Conclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.
LanguageEnglish
Pages488-494
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume65
Issue number4
DOIs
StatusPublished - Apr 2006

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Lymphotoxin-alpha
Systemic Lupus Erythematosus
Haplotypes
HLA-DR3 Antigen
Tumor Necrosis Factor-alpha
Genes
Odds Ratio
Polymorphism
HLA-DR7 Antigen
Nucleotides
HLA-DR2 Antigen
HLA-DRB1 Chains
Polymerase chain reaction
Single Nucleotide Polymorphism
Alleles
HLA-DQB1 antigen
Case-Control Studies
Confidence Intervals
Polymerase Chain Reaction

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MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus. / McHugh, N J; Owen, P; Cox, B; Dunphy, J; Welsh, K.

In: Annals of the Rheumatic Diseases, Vol. 65, No. 4, 04.2006, p. 488-494.

Research output: Contribution to journalArticle

@article{0b164283bd884004ae1fa19c624a4dfe,
title = "MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus",
abstract = "Objective: To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE. Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. Results: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95{\%} confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13{\%}) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303; DRB1*0701/2; TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)). Conclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.",
author = "McHugh, {N J} and P Owen and B Cox and J Dunphy and K Welsh",
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TY - JOUR

T1 - MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus

AU - McHugh, N J

AU - Owen, P

AU - Cox, B

AU - Dunphy, J

AU - Welsh, K

PY - 2006/4

Y1 - 2006/4

N2 - Objective: To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE. Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. Results: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303; DRB1*0701/2; TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)). Conclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.

AB - Objective: To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE. Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. Results: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303; DRB1*0701/2; TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)). Conclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.

UR - http://dx.doi.org/10.1136/ard.2005.039842

U2 - 10.1136/ard.2005.039842

DO - 10.1136/ard.2005.039842

M3 - Article

VL - 65

SP - 488

EP - 494

JO - Annals of the Rheumatic Diseases

T2 - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 4

ER -