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Basic & Translational Science

Category: Chlamydia

(P10) HLA-DQB1*06 and Select Neighboring HLA Variants Predict Chlamydia Reinfection Risk

Tuesday, July 25, 2023
16:00 – 18:00 CST


Background: Chlamydia remains highly prevalent. Immunogenetic determinants impact chlamydia risk. We previously established an association of HLA-DQB1*06 with reinfection risk in two distinct cohorts. However, these association studies do not establish DQB1*06 as a genetic variant driving chlamydia outcomes because of possible linkage disequilibrium (LD) with neighboring HLA variants. Our study aimed to determine whether HLA-DQB1*06 and/or neighboring HLA variants in LD strongly predicted reinfection risk.



Methods: Using DNA from 185 African American chlamydia-infected women with vs. without chlamydia reinfection at follow-up, the chromosome 6 region HLA-DRA through HLA-DQB1 was captured using custom oligos (Agilent) and subjected to paired end 150bp sequencing on the Illumina NextSeq500 to determine HLA variants and local haplotypes contributing to reinfection risk. We used the Sequence Kernel Association Test (SKAT) on moving windows throughout entire genes in the sequenced region and on gene regions defined by adjacent exon/intron pairs to test for association between haplotypes and reinfection. Age, African ancestry, and presence of both DQB1*06 and DQB1*04 alleles were included as predictors (either because of univariate associations with reinfection or a priori).



Results: Chlamydia reinfection occurred in 38 (20%) women and both DQB1*06 and DQB1*04 were significantly associated with reinfection (P=0.0025 and P=0.0049, respectively). One window of 50 variants in the HLA-DRB5 gene (size 1033 bp) showed significant association with reinfection (P=0.0051), as did a smaller window of 20 variants (size 58 bp) in DRB5 (P=0.0051). There were also windows in the HLA-DRA gene associated with reinfection at a higher significance threshold (P value between 0.01-0.05).



Conclusion: We verified that HLA-DQB1*06 as well as DQB1*04 and neighboring variants (haplotypes) in the DRB5 and DRA genes were associated with chlamydia reinfection. Future studies will address underlying functional mechanisms through which these genetic variants increase chlamydia reinfection risk.