Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.
BACKGROUND
Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities.


OBJECTIVE
To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population.


METHODS
Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls.


RESULTS
We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively).


CONCLUSIONS
IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.
Yamamoto-Furusho
Jesús K
JK
Department of Gastroenterology, Inflammatory Bowel Disease Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.
Santiago-Hernández
Jean J
JJ
Pérez-Hernández
Nonanzit
N
Ramírez-Fuentes
Silvestre
S
Fragoso
José Manuel
JM
Vargas-Alarcón
Gilberto
G
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta