Systemic lupus erythematosus candidate genes in the Italian population: evidence for a significant association with interleukin-10.
OBJECTIVE
To determine whether 7 candidate genes, including tumor necrosis factor receptor II, bcl-2, CTLA-4, interleukin-10 (IL-10), CD19, Fcy 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; chi2y = 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; chi2y = 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 according to the presence of the associated HLA-DR or IL-10 alleles.


CONCLUSIONS
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.
D'Alfonso
S
S
Università del Piemonte Orientale A. Avogadro, Novara, Italy.
Rampi
M
M
Bocchio
D
D
Colombo
G
G
Scorza-Smeraldi
R
R
Momigliano-Richardi
P
P
D000069594:Abatacept; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D018941:Antigens, CD19 / Q000235:genetics; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D018796:Immunoconjugates; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000235:genetics*; D007558:Italy; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C080568:Fc gamma receptor IIA; D005819:Genetic Markers; C507763:IL1RN protein, human; D018796:Immunoconjugates; D053590:Interleukin 1 Receptor Antagonist Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D016753:Interleukin-10; D000069594:Abatacept