Rs7574865

rs7574865, a SNP in the third intron of the STAT4 gene, has been reported in a large study of Swedes to be associated with both rheumatoid arthritis (RA) and lupus (SLE). Among other studies, it has been confirmed in a meta-analysis of 8 studies totaling 7,381 patients and over 10,000 controls from both European and Asian populations.

The risk allele (oriented to the dbSNP entry) is (T); the odds ratio associated the presence of a risk allele was 1.3 for rheumatoid arthritis and 1.55 for lupus (SLE). The paper states that, "Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis."

A study of 124 Caucasian patients with primary Sj&, an autoimmune disease related to RA and SLE, also found the rs7574865(T) allele to be associated with higher risk for this condition (p=0.01). The GT genotype is associated with 1.42x and the TT with 2.28x odds.

associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19)), nephritis (MAF = 34.3%, OR = 1.80, p<10(-11)), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13))

The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 x 10(-9)) and 1.61 (P = 2.1 x 10(-11)) for allele frequency distribution; these ORs in the Japanese were quite similar to those previously observed in the Caucasian population

RA risk associated with rs7574865(T) allele was also found in studies of 923 Spanish, 273 Swedish, and 876 Dutch patients.

The rs7574865(T) allele is associated with increased risk for type-1 diabetes; the odds ratio is 1.94, CI: 1.29-2.91, p = 0.0012, based on a study of Greek patients.

A study of RA patients from Crete also found that the rs7574865(T) allele represented increased risk for rheumatoid arthritis.

A study of 2,776 Spanish subjects found that the rs7574865(T) allele was associated with rheumatoid arthritis, Crohn's disease, ulcerative colitis, and type-1 diabetes, but not with multiple sclerosis.

Scleroderma