TY - JOUR
T1 - Systemic lupus erythematosus candidate genes in the Italian population
T2 - Evidence for a significant association with interleukin-10
AU - D'Alfonso, Sandra
AU - Rampi, Marco
AU - Bocchio, Daniela
AU - Colombo, Gualtiero
AU - Scorza-Smeraldi, Raffaella
AU - Momigliano-Richiardi, Patricia
PY - 2000/1
Y1 - 2000/1
N2 - Objective. To determine whether 7 candidate genes, including tumor necrosis factor receptor II, bcl-2, CTLA-4, interleukin-10 (IL-10), CD19, Fcγ receptor type IIA (CD32), and IL-1 receptor antagonist, may contribute to susceptibility to systemic lupus erythematosus (SLE) in the Italian population. Methods. The association with SLE of intragenic markers for each candidate gene, including either microsatellites or dimorphisms, was analyzed. Gene frequencies of these gene markers were compared for patients and ethnically matched controls. Significance was tested by chi-square test on 2 x 2 tables and by Monte Carlo simulation on 2 x N tables. Results. A significant increase was found in SLE patients (0.170 versus 0.095; χ2(y) = 4.11, P = 0.0425) in the frequency of the 140-basepair allele of the IL10.G microsatellite located in the promoter region of the IL-10 gene. This finding was confirmed in a second independent panel where, again, the frequency of the 140-bp allele was found to be significantly increased in SLE patients versus controls (0.176 versus 0.086; χ2(y) = 3.95, P = 0.0470). Considering the 2 panels together, the relative risk conferred by the presence of the 140-bp allele was 1.78 (95% confidence interval 1.19-2.66). Conversely. no significant association was detected for the remaining 6 candidate genes, even when the patients were stratified according to the presence of different clinical and immunologic features or according to the presence of the associated HLA-DR or IL-10 alleles. Conclusion. Of the 7 candidate genes tested, only IL-10 was significantly associated with SLE in Italian patients. This genetic marker represents, apart from HLA, the only genetic susceptibility factor for SLE found so far in the Italian population.
AB - Objective. To determine whether 7 candidate genes, including tumor necrosis factor receptor II, bcl-2, CTLA-4, interleukin-10 (IL-10), CD19, Fcγ receptor type IIA (CD32), and IL-1 receptor antagonist, may contribute to susceptibility to systemic lupus erythematosus (SLE) in the Italian population. Methods. The association with SLE of intragenic markers for each candidate gene, including either microsatellites or dimorphisms, was analyzed. Gene frequencies of these gene markers were compared for patients and ethnically matched controls. Significance was tested by chi-square test on 2 x 2 tables and by Monte Carlo simulation on 2 x N tables. Results. A significant increase was found in SLE patients (0.170 versus 0.095; χ2(y) = 4.11, P = 0.0425) in the frequency of the 140-basepair allele of the IL10.G microsatellite located in the promoter region of the IL-10 gene. This finding was confirmed in a second independent panel where, again, the frequency of the 140-bp allele was found to be significantly increased in SLE patients versus controls (0.176 versus 0.086; χ2(y) = 3.95, P = 0.0470). Considering the 2 panels together, the relative risk conferred by the presence of the 140-bp allele was 1.78 (95% confidence interval 1.19-2.66). Conversely. no significant association was detected for the remaining 6 candidate genes, even when the patients were stratified according to the presence of different clinical and immunologic features or according to the presence of the associated HLA-DR or IL-10 alleles. Conclusion. Of the 7 candidate genes tested, only IL-10 was significantly associated with SLE in Italian patients. This genetic marker represents, apart from HLA, the only genetic susceptibility factor for SLE found so far in the Italian population.
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U2 - 10.1002/1529-0131(200001)43:1<120::AID-ANR15>3.0.CO;2-3
DO - 10.1002/1529-0131(200001)43:1<120::AID-ANR15>3.0.CO;2-3
M3 - Article
C2 - 10643707
AN - SCOPUS:0034121689
VL - 43
SP - 120
EP - 128
JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association
JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association
SN - 0893-7524
IS - 1
ER -