학술논문
Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study.
Document Type
Article
Author
Schwenke, Johannes M; Thorball, Christian W; Schoepf, Isabella C; Ryom, Lene; Hasse, Barbara; Lamy, Olivier; Calmy, Alexandra; Wandeler, Gilles; Marzolini, Catia; Kahlert, Christian R; Bernasconi, Enos; Kouyos, Roger D; Günthard, Huldrych F; Ledergerber, Bruno; Fellay, Jacques; Burkhalter, Felix; Tarr, Philip E; Study, for the Swiss HIV Cohort
Source
Subject
*DISEASE risk factors
*MONOGENIC & polygenic inheritance (Genetics)
*HIV-positive persons
*DUAL-energy X-ray absorptiometry
*OSTEOPOROSIS
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Language
ISSN
0022-1899
Abstract
Background Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. Methods Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011–2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. Results We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34–9.67) and 4.13 (1.86–9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37–3.74), 1.84 (1.40–2.43), and 1.54 (0.82–2.9). Conclusions In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate. [ABSTRACT FROM AUTHOR]