Strong combined gene–environment effects in anti–cyclic citrullinated peptide–positive rheumatoid arthritis: A nationwide case–control study in Denmark

Abstract

Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.