Association between common telomere length genetic variants and telomere length in an African population and impacts of HIV and TB

Abstract

Prior studies in predominantly European (Caucasian) populations have discovered common genetic variants (single nucleotide polymorphisms, SNPs) associated with leukocyte telomere length (LTL), but whether these same variants affect LTL in non-Caucasian populations are largely unknown. We investigated whether six genetic variants previously associated with LTL (TERC (rs10936599), TERT (rs2736100), NAF1 (7675998), OBFC1 (rs9420907), ZNF208 (rs8105767), and RTEL1 (rs755017)) are correlated with telomere length (TL) in peripheral blood mononuclear cells (PBMCs) in a cohort of Africans living with and without HIV and undergoing evaluation for tuberculosis (TB). We found OBFC1 and the genetic sum score of the effect alleles across all six loci to be associated with shorter TL (adjusted for age, gender, HIV status, and smoking pack-years (p < 0.02 for both OBFC1 and the genetic sum score). In an analysis stratified by HIV status, the genetic sum score is associated with LTL in both groups with and without HIV. On the contrary, a stratified analysis according to TB status revealed that in the TB-positive subgroup, the genetic sum score is not associated with LTL, whereas the relationship remains in the TB-negative subgroup. The different impacts of HIV and TB on the association between the genetic sum score and LTL indicate different modes of modification and suggest that the results found in this cohort with HIV and TB participants may not be applied to the African general population. Future studies need to carefully consider these confounding factors.

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Acknowledgements

This work was supported by the National Institutes of Health (grant numbers R01 HL128156, R01 HL090335, K24 HL087713, and D43 TW009607). The funding sources played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. We wish to acknowledge the participants of this study, the hospital staff at Mulago National Referral Hospital in Kampala, Uganda, and the following individuals: Alfred Andama, Catherine Nabakiibi, Sylvia Kaswabuli, Robert Ssebunya, Dr. Irene Ayakaka, Dr. Wallen Tumwine, Priscilla Bbosa, Yusef Magezi, Josephine Zawedde, Dr. Elizabeth Blackburn, Colin Huang, Serena Fong, Stephen Stone, Elizabeth Auld, Alisa Malki, Marlena Hartman-Filson, Maggie McGing, and Mathew Sommers.

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Correspondence to Jue Lin.

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JL is a co-founder and scientific advisor to Telomere Diagnostic Inc. The company played no role in this study. Other authors declare that they have no conflict of interest.

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Wang, S., Chang, E., Byanyima, P. et al. Association between common telomere length genetic variants and telomere length in an African population and impacts of HIV and TB. J Hum Genet 64, 1033–1040 (2019). https://doi.org/10.1038/s10038-019-0646-9

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