Τετάρτη 9 Νοεμβρίου 2022

Obesity-related SNPs and weight gain following first-line antiretroviral therapy

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Abstract
Background
We studied the association of obesity-related SNPs (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with HIV (PWH).
Methods
Participants were ART-naïve PWH from the Spanish HIV Research Cohort who started ART from 2014 onwards and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of GWAS body mass index (B MI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models (A-LMM).
Results
A total of 1,021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% CI: 2.54–3.26) Kg. Factors associated with higher weight gain were female sex, birth in Sub-Saharan Africa, prior AIDS, CD4+ < 200 cells/uL, HIV-RNA > 100,000 copies/mL, negative HCV serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotypes polymorphisms and weight and BMI increase. The estimated adjusted mean (SE) of weight gains were 4.26 (0.56) Kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) Kg in AA/AG carriers (P = 0.007). Likewise, the estimated means (SE) weight gain at 96 weeks were 3.35 (0.29) Kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) Kg in AG/AA carriers (P = 0.020).
Conclusions
Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.
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