This variant was reported to be associated with autoimmune disease when homozygous. However, a later publication has contradicted this result, finding no significant association between this variant and autoimmune disease in a very large cohort.
This paper implicates this polymorphism as potentially contributing to autoimmune diseases when homozygous. The variant was seen homozygously in 8 out of 923 cases and 0 out of 648 controls. Using two-tailed Fisher’s Exact, this is p = 0.024. However, because there are several other polymorphisms, multiple hypotheses were implicitly being tested and so we give this a case/control significance of 1 point (0.1 < p < 0.05). The overall allele frequency of the variant in controls is 0.049, they list four other variants with allele frequencies > 0.025.
They report that the protein product with this variant is catalytically active but is not secreted. This finding was reproduced in a pulse-chase experiment with 35S-methionine.
This data suggests homozygosity for this variant explains ~1% of autoimmune cases. An allele frequency of 0.049 implies that .24% of people are homozygous for this variant. Assuming an incidence of autoimmune disease in 1 out of 50 people, 0.02% of people would be expected to have autoimmune disease that might be attributed to this variant — this puts an estimate of penetrance for autoimmune disease in the homozygous individuals at ~8% (.02 / .24), approximately fourfold relative risk and ~6% attributable increased risk.
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