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

Abstract

AbstractBackgroundHeme 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.MethodsParticipants 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.ResultsNearly 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.ConclusionsA 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.