Interleukin-12 gene polymorphisim in patients with giant cell arteritis, polymyalgia rheumatica and elderly-onset rheumatoid arthritis.
OBJECTIVE
The cytokine profile suggests that giant cell arteritis (GCA) is a Th1-driven disease, in which local IFN-gamma plays a critical role in the development of a systemic arteritis. IL-12 is a potent inducer of IFN-gamma and is critically involved in biasing an immune response towards a Th1 pathway. The purpose of this study was to investigate whether there was an association between an IL-12 gene polymorphism (-1188 A/C 3UTR) and disease susceptibility for GCA and two other age-related inflammatory conditions, such as polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA). Furthermore, we attempted to correlate such polymorphism with in vitro IL-12 production.


METHODS
We analyzed genotypes at -1188 in the 3UTR of the IL-12 promoter by PCR-RFLP in 68 GCA, 138 PMR, and 72 EORA patients as well as in 465 healthy controls (HC). IL-12p70 levels in culture supernatants after stimulation with PMA+Ionomycin was assessed by ELISA.


RESULTS
All groups were in Hardy-Weinberg equilibrium. Allelic and gen-omic distribution was not significantly different among the study groups. None of the genetic variants was associated with disease severity. Although the differences were not statistically significant, HC genotypes were associated with distinct IL-12 p70 production.


CONCLUSIONS
The IL-12 (-1188 A/C 3UTR) gene polymorphism is not associated with disease susceptibility or severity in three age-related chronic inflammatory syndromes. The production of IL-12 p70 is dependent on the genetic background in HC, although in patients such association may be biased by other unknown factors.
Alvarez-Rodriguez
L
L
Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Martínez-Taboada
V M
VM
López-Hoyos
M
M
Mata
C
C
Fernandez Prieto
L
L
Agudo-Bilbao
M
M
Calvo
J
J
Ruiz Soto
M
M
Rodriguez-Valverde
V
V
Ruiz
T
T
Blanco
R
R
Corrales
A
A
Carrasco-Marín
E
E
D020413:3' Untranslated Regions / Q000235:genetics*; D000368:Aged; D000375:Aging / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011111:Polymyalgia Rheumatica / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
D020413:3' Untranslated Regions; D018664:Interleukin-12