Heme Oxygenase-1 Promoter (GT)n Alleles and Neurocognitive Functioning in Thai Youth with Perinatally-Acquired HIV: A Pilot Study

Background Heme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may modify HIV-associated neurocognitive impairment (HIV-NCI) risk. Among adults, short HO-1 (GT)n alleles associate with greater HO-1 antioxidant enzyme inducibility and lower rates of HIV-NCI. This pilot study examined associations between HO-1 (GT)n alleles and neurocognitive outcomes in a sample of Thai youth (13-23 years) with perinatally-acquired HIV (PHIV) and demographically-matched HIV-negative controls. Methods Participants completed neurocognitive testing and provided blood samples for DNA extraction and sequencing of HO-1 promoter (GT)n dinucleotide repeat lengths. Allele lengths were assigned based on number of (GT)n repeats: <27 Short (S); 27-34 Medium (M); >34 Long (L). Relationships between HO-1 (GT)n repeat lengths and neurocognitive measures were examined, and differences by HO-1 (GT)n allele genotypes were explored. Results Nearly half (48%) of all HO-1 (GT)n promoter alleles were short. Longer repeat length of participants’ longest HO-1 (GT)n alleles significantly associated with poorer processing speed (Total sample: r =-.36, p =.01; PHIV only: r =-.69, p <.001). Compared to peers and controlling for covariates, SS/SM genotypes performed better in processing speed, and SS genotypes performed worse in working memory. Conclusions A high frequency of short HO-1 (GT)n alleles was found among these Thai youth, as previously observed in other cohorts of people of Asian ancestry. In contrast to previous adult studies, the presence of a short allele alone did not associate with better neurocognitive performance, suggesting additional modifying effects among the different alleles. Research is needed to determine whether HO-1 (GT)n promoter genotypes differentially influence neurocognitive functioning across the lifespan and different ethnic backgrounds. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Columbia University's and the New York State Psychiatric Institute's HIV Center for Clinical and Behavioral Studies, a program funded by the National Institute of Mental Health (P30 MH043520, PI: Remien). This work was also supported by funding from a training grant from the National Institute of Mental Health (T32 MH019139, PI: Sandfort) and funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21 HD098035, PI: Robbins). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the New York State Psychiatric Institute's IRB and the Research Institute For Heath Sciences, Chiang Mai University's Human Experimentation Committee. Written informed consent was collected from participants >18 years. For participants <18 years, participant assent and written informed consent from a parent/guardian were collected. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.