Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania.

BACKGROUND: Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients. METHODS: This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy. RESULTS: We are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis. CONCLUSIONS: This study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

Impaired fasting glucose levels among perinatally HIV-infected adolescents and youths in Dar es Salaam, Tanzania.

Objective: This study assessed impaired fasting glucose and associated factors among perinatally HIV-infected adolescents and youths in Dar es salaam Tanzania. Background: Impaired fasting glucose is a marker of heightened risk for developing type 2 diabetes among perinatally HIV-infected individuals. Therefore, identifying individuals at this stage is crucial to enable early intervention. Therefore, we assessed impaired fasting glucose (IFG) and associated factors among perinatally HIV-infected population in Dar es salaam Tanzania. Methods: A cross-sectional study was conducted among 152 adolescents and youth attending HIV clinic at Muhimbili National Hospital and Infectious Disease Centre from July to August 2020. Fasting blood glucose (>8 hours) was measured using one-touch selects LifeScan, CA, USA. We also examined C-Reactive Protein and interleukin-6 inflammatory biomarkers in relation to impaired fasting glucose (IFG). Associations between categorical variables were explored using Chi-square, and poison regression with robust variance was used to calculate the prevalence ratios. Results: Of the 152 participants, the majority were male (n=83[54.6%]), and the median age was 15(14-18) years. Overweight or obesity was prevalent in 16.4%, while more than one in ten (13.2%) had high blood pressure (≥149/90mmHg). All participants were on antiretroviral therapy (ART); 46% had used medication for over ten years, and about one in three had poor medication adherence. Among the recruited participants, 29% had impaired fasting glucose. The odds of IFG were two times higher in males compared to females (PR, 2.07, 95% CI 1.19 -3.59 p=0.001). Moreover, we found with every increase of Interleukin 6 biomarker there was a 1.01 probability increase of impaired fasting glucose (PR, 1.01, 95% CI 1.00 - 1.02 p=0.003). Conclusion: About one in three perinatally HIV-infected youths had impaired fasting glucose in Dar es Salaam, Tanzania, with males bearing the biggest brunt. Moreover, with every increase of 1.101 of the probability of having IFG increased. This calls for urgent measures to interrupt the progression to diabetes disease and prevent the dual burden of disease for this uniquely challenged population.