JCEM-jc-2018-01974-KAHALY-SUPPLEMENTAL-TABLES.pdf

<b>Context</b>: The Major Histocompatibility Complex (MHC) strongly contributes to the development of polyglandular autoimmunity (PGA). <b>Objective</b>: To evaluate the impact of gender on human leukocyte antigen (HLA) association with PGA for the first time. <b>Design</b>: Cross-sectional immunogenetic study <b>Setting</b>: Academic, tertiary referral, orphan disease center for PGA (ORPHA 282196) and immunogenetics laboratory <b>Subjects</b>: 158 patients with coexistent type 1 diabetes and autoimmune thyroid disease (adult type three PGA, ORPHA 227982) and 479 unrelated healthy controls <b>Methods: </b>All 637 subjects were typed for HLA-A, -B, DRB1, -DQA1, and –DQB1 alleles at a two-field level.<b> </b> <b>Main outcome measure</b>: Modification of the gene-disease association by gender <b>Results</b>: MHC class I <i>HLA-A</i> association was gender-related to both the total adult type three PGA collective (n=158, <i>p</i>=0.0065) as well as in PGA patients with autoimmune Hashimoto’s thyroiditis (n=91, <i>p</i>=0.010). Compared to HLA-A*02:01, <i>A*11:01</i> was overrepresented in male patients, yet underrepresented in females (OR 1.49, 95% CI 0.55-3.88 vs. 0.42, 0.12-1.17). A<i>*24:02</i> was underrepresented in males but not in female patients (OR 0.37, 95% CI 0.111.04 vs. 1.19, 0.65-2.15). Excluding the five most frequent alleles (A*01:01, A*02:01, A*03:01, A*11:01, and A*24:02), the sum of all other identified alleles was underrepresented in male patients (OR 0.37, 0.18-0.72, <i>p</i>=0.0046). The strong MHC HLA-B association with PGA (<i>p</i>&lt;0.0001) was not gender-related (<i>p</i>=0.55). Further, no interaction with gender was observed for the MHC class II <i>HLA-DRB1</i>, <i>DQA1,</i> and <i>DQB1</i> alleles. <b>Conclusion</b>: MHC class I<i> HLA-A </i>association with type three PGA is significantly affected by gender.