Influence of interleukin-1 receptor antagonist gene polymorphism on disease.
Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring competitive inhibitor of interleukin-1 (IL-1)-induced proinflammatory activity. The IL-1RA gene is polymorphic, resulting in quantitative differences in both IL-1RA and IL-1beta production. Persons homozygous for allele 2 of the IL-1RA gene (IL1RN*2) have a more prolonged and more severe proinflammatory immune response than persons with other IL-1RA genotypes. Thus, being IL1RN*2 homozygous might be beneficial when combating infectious agents or malignantly transformed cells, but it might be detrimental for those with chronic inflammatory conditions or who are pregnant. The IL1RN*2 phenotype is associated with ulcerative colitis and Crohn's disease, lupus erythematosus, vulvar vestibulitis, and possibly with osteoporosis and coronary artery disease. IL1RN*2 homozygosity may also be associated with recurrent spontaneous abortion, preterm birth, and severity of preeclampsia. Conversely, there are negative associations between IL1RN*2 homozygosity and vaginal colonization with mycoplasmas, infection with human cytomegalovirus and Epstein-Barr virus, human immunodeficiency virus proliferation, and the occurrence of ovarian cancer.
Witkin
Steven S
SS
Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, NY 10021, USA. switkin@mail.med.cornell.edu
Gerber
Stefan
S
Ledger
William J
WJ
D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D011110:Polymorphism, Genetic / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins