Association of polymorphisms in the IL1B and IL2 genes with susceptibility and severity of systemic sclerosis.
OBJECTIVE
To investigate possible associations of 9 single-nucleotide polymorphisms in the IL10, IL1B, IL1A, IL1RN, IL2, LTA, and IL6 genes with susceptibility to systemic sclerosis (SSc), and with clinical subtype of SSc patients.


METHODS
A total of 78 patients with SSc [diffuse SSc (dcSSc), n = 31; limited SSc, (lcSSc), n = 47] and 692 healthy blood donors were genotyped for the following polymorphisms: IL10 T-3575A, IL10 A-1082G, IL1B C-31T, IL1B C-511T, IL1A C-889T, IL1RN A9589T, IL2 T-384G, LTA T-91G, and IL6 G-174C.


RESULTS
Alleles in IL1B-31 and IL1B-511 showed a significantly different distribution between cases and controls. Carriers of at least one copy of the IL1B-31-C allele had an increased risk of SSc [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-5.2, p < 0.001], while a similar strong association was also evident for IL1B-511-T carriers (OR 3.1, 95% CI 1.7-5.7, p < 0.001). Interestingly, carriers of the IL2-384-G allele were significantly more frequent among patients with lcSSc (80.8%), compared to patients with the diffuse subtype (45.1%) (OR 5.1, 95% CI 1.8-14.3, p = 0.001) and in subjects positive to anticentromere antibodies (OR 4.2, 95% CI 1.5-11.9, p = 0.007). Lastly, the distribution of the IL2-384 genotype showed statistically significant differences between controls and patients with lcSSc (OR 3.5, 95% CI 1.7-7.4, p < 0.001). There were no differences between patients with dcSSc and controls.


CONCLUSIONS
IL1B and IL2 gene polymorphisms may be involved in susceptibility to SSc. Moreover, the IL2-384-G allele may be a marker for the limited phenotype of SSc.
Mattuzzi
Silvia
S
Dipartimento di Patologia, Universita di Verona, Verona, Italy.
Barbi
Stefano
S
Carletto
Antonio
A
Ravagnani
Viviana
V
Moore
Patrick S
PS
Bambara
Lisa Maria
LM
Scarpa
Aldo
A
D000328:Adult; D018771:Arthralgia / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D001168:Arthritis / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D015415:Biomarkers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011658:Pulmonary Fibrosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D045745:Scleroderma, Limited / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
D015415:Biomarkers; C508585:IL1B protein, human; C508594:IL2 protein, human; D053583:Interleukin-1beta; D007376:Interleukin-2