TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus.
OBJECTIVE
To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE).


METHODS
TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes.


RESULTS
The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRBI*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation.


CONCLUSIONS
TNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.
Rood
M J
MJ
Leiden University Medical Center, The Netherlands.
van Krugten
M V
MV
Zanelli
E
E
van der Linden
M W
MW
Keijsers
V
V
Schreuder
G M
GM
Verduyn
W
W
Westendorp
R G
RG
de Vries
R R
RR
Breedveld
F C
FC
Verweij
C L
CL
Huizinga
T W
TW
D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha