A Haptoglobin Exon Copy Number Variant Associates With HIV-Associated Neurocognitive Impairment in European and African-Descent Populations

• DOI: 10.3389/fgene.2021.756685
• Publication Date: 2021-12-22T06:24:43Z
• Authors: Haimeng Bai; Harpreet Kaur; Asha R. Kallianpur; Todd Hulgan; Donald R. Franklin; Scott L. Letendre; Ronald J. Ellis; William S. Bush
• Keywords: Neurocognitive; Haptoglobin; African descent

A common two-exon deletion distinguishes the gene encoding free hemoglobin capturing protein-haptoglobin (HP)-into two alleles: HP1 and HP2. To evaluate impact of this copy number variant (CNV) on neurocognitive impairment (NCI) in people living with HIV, we imputed 432 European-descent (EUR) 491 African-descent (AFR) participants from CNS HIV Antiretroviral Therapy Effects Research Study using an optimized imputation pipeline evaluated its associations NCI. At baseline, AFR, HP2 allele decreased odds NCI (defined by a global deficit score, GDS, ⩾0.5 ; Odds Ratio, OR = 0.584, p 0.022). However, EUR, increased (OR 2.081, 0.040) suggesting detrimental effect. These effects were extended to longitudinal analyses repeated measurements where protective effect AFR became marginally significant (p 0.054) EUR significance 0.037). In slightly reduced risk over time 0.028 per year, 0.024). Further cognitive domain-specific revealed that HP-NCI was based changes learning, speed information processing, verbal domains differing ancestry groups. Overall, these findings suggest functional HP CNV alleles influence likelihood contribute function HIV.