Genetic architecture of cardiometabolic risks in people living with HIV

Abstract

Background Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. Methods We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. Results We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. Conclusions Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Cardiovascular risk assessment in people living with HIV compared to the general population

“…Further refinements may also be based on integrating genetic data into risk estimation. 28 Limitations should be considered while interpreting our results. F i r s t ,o u ra n a l y s i si sb a s e do no b s e r v a t i o n a ld a t aa n dw ed i dn o ta ccount for medical interventions that might have changed ASCVD development.…”

Associations between female birth sex and risk of chronic kidney disease development among people with HIV in the USA: A longitudinal, multicentre, cohort study

“…Genotyping was performed using the expanded Illumina Multi-Ethnic Genotyping Array as described elsewhere. 34 Single nucleotide polymorphisms (SNPs) with call rates < 95%, minor allele frequency < 5%, deviation from Hardy-Weinberg equilibrium (p-value < 1 × 10 −29 ), and regions of high linkage disequilibrium (LD), 35 as well as samples with call rates < 95%, sex discrepancies between genotype data and self-report, and pairwise identity- by- descent (‘pi-hat’) > 0·9 were excluded as implemented in Plink v1·9. 36 For linkage disequilibrium pruning, linked SNPs were removed using r 2 ≥ 0·1.…”

Anthropometric Profile of Patients Living With Hiv/Aids in Lviv Region

“…The evidence that waist circumference, waist-toheight ratio, and waist to hip ratio are independent predictors of cardiac risk and metabolic syndrome and are, therefore, important for HIV / AIDS patients receiving antiretroviral therapy, dictated the choice of anthropometric parameters. [12].…”