Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry

Abstract

No Abstrac

Lack of association between rare mutations of the SIAE gene and rheumatoid arthritis in a Han Chinese population

“…Szymański et al (2011) tested the homozygous Met89Val substitution of SIAE in patients with Graves' disease (GD) and type 1 diabetes mellitus (T1DM) patients in a Polish population. Hunt et al (2011) replicated and extended the SIAE findings of Surolia et al (2010) in a much larger independent study of autoimmune and chronic immune diseases. However, Hunt et al's results illustrated that rare and functional SIAE variants are not associated with autoimmune disease risk.…”

“…This study highlighted the fact that the strong effect of defective SIAE variants on susceptibility to autoimmunity needs to be investigated further. Moreover, Hunt et al (2011) in 66,924 samples from five ethnic groups with autoimmune diseases and found homozygotes of the variant in all cases and controls. The variant encoding SIAE p.Met89Val was genotyped in 4805 offspring-parent trios of European origin in five autoimmune diseases.…”

“…The study found no evidence indicating an effect of the p.Met89Val alteration on autoimmune disease risk. An analysis of eight additional rare SIAE variants in 43,378 subjects identified no functional SIAE variants as potential factors for autoimmune disease risk (Hunt et al,2011). Finally, Gan et al (2012) analyzed nine SIAE gene variants in a UK cohort of 378 subjects with autoimmune Addison's disease (AAD) and 387 healthy controls.…”

“…Genomic DNA was prepared from peripheral leukocytes as described previously (Hunt et al, 2011). Table 2 lists the primers used to amplify the coding exons and adjacent introns of SIAE (NCBI human genome build 36.3, NC_000011.9 for genomic DNA, NM_032811.2 for mRNA, and NP_001186851.1 for proteins).…”

Face up to false positives

“…For instance, rare loss-of-function mutations in a gene called SIAE were reported to have a large effect on the risk of autoimmune diseases 4 . But a later, combined analysis of more than 60,000 samples 5 showed no evidence of an association, suggesting that the finding in the original publication was down to chance. Key results in the retracted genetic analysis of longevity mentioned earlier 1 turned out to be errors that arose as a result of combining data from multiple genotyping platforms.…”