Browsing by Autor "Victor R. Gordeuk"

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Acute promyelocytic leukemia incidence in Andean highlanders with the NFKB1 haplotype (rs230511)
(Elsevier BV, 2025) Ricardo Amaru; Victor R. Gordeuk; Julieta Luna; Edgar Teddy Quispe Soto; Silvia Mancilla; Javier Valencia; Luis Felipe Mamani; Daniela Patón; Ariel Amaru
Abstract Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), characterized by the oncogenic fusion protein PML-RARα, which results from the t(15;17) chromosomal translocation. APL accounts for approximately 4-10% of AML cases worldwide. The median age at diagnosis falls around the fifth decade of life, with a slight male predominance (PMID: 39682277). The PML-RARα fusion protein plays an essential role in the pathogenesis of APL by enhancing hypoxia-inducible factor (HIF)-driven transcriptional activity. PML-RARα acts as a transcriptional co-activator of HIF-α, amplifying HIF-mediated transcription independently of PML protein inhibition. This activation is unique to APL-specific fusion proteins; it is absent in other AML subtypes. The interaction of PML-RARα and HIF factors significantly influences disease progression and relapse. (PMID: 24711541). Transcriptomic analyses of APL cells reveal enrichment of NF-κB signaling pathways among differentially expressed genes, particularly those involved in cancer pathways. This suggests that NFKB1 contributes to the proliferative and survival signaling in APL cells (Villiers W, Nat. Commun, 2023). However, PML-RARα disrupts NF-κB activity by inhibiting phosphorylation and DNA binding of the NF-κB p65 subunit, suppressing NF-κB target gene expression. This disruption contributes to leukemogenesis through impaired differentiation and altered transcriptional regulation (Ahmed A, Sci.rep, March 2017). The incidence of APL varies across geographic regions and ethnic groups. Higher frequencies have been observed in Latin American populations compared to North America and Europe. These disparities suggest that genetic and environmental factors contribute to differences in disease distribution and outcomes (PMID: 12935956) and currently, there are no published data directly comparing APL incidence between populations living at sea level and those residing at high altitudes. We investigated the proportion of AML cases diagnosed as APL in Bolivian Andean highlanders residing at 4000 m, a population characterized by elevated HIF-α expression and a predominant NFKB1 haplotype rs230511 (95%) that results in a non-functional NFKB1 protein. We then compared the proportion of APL cases from Bolivian populations living at 2000m and 400 m. We analyzed 1,273 AML diagnoses from January 2000 to June 2025, grouped by altitude of residence: 406 at 4,000 m (mean age 37 years), 412 at 2,000 m (mean age 41 years), and 455 at 400 m (mean age 28 years). The overall mean age at AML diagnosis was 35 ± 25 years, with a male predominance of 54%. Among the total AML cases, 140 (11.0%) were identified as APL. We compared the proportion of AML cases classified as APL across three altitudes: at 4,000 m, 38 of 406 AML cases (9.4%) were APL; at 2,000 m, 46 of 412 cases (11.2%); and at 400 m, 56 of 455 cases (12.3%). There was a trend toward a lower proportion of APL cases at 4,000 m compared to 2,000 m and 400 m, although this difference was not statistically significant (P = 0.17). The age distribution of APL cases was as follows: 1-17 years, 44 cases (31.4%); 18-39 years, 59 cases (41.7%); 40–59 years, 30 cases (21.4%); and ≥60 years, 7 cases (5.0%). The age of AML patients was significantly lower at 400 m compared to the higher altitudes, whereas the proportion of males did not differ significantly by altitude. ConclusionsThe APL tends to decrease with increasing altitude, consistent with genetic adaptations in high-altitude Andean populations (~4000 m) involving increased HIF activity and a specific NFKB1 haplotypeThe 25-year incidence of APL was significantly lower in the La Paz population at 4000 m compared to populations at lower elevations (P &lt; 0.020).Individuals younger than 40 years are disproportionately affected, representing 73.1% of APL cases. The increased incidence in younger age groups does not vary by altitude, suggesting that genetic factors may predominantly drive this demographic pattern.Investigating genetic adaptations in high-altitude populations could offer novel insights into APL pathobiology and therapeutic strategies.
Aminothiol Multidentate Chelators against Chagas Disease
(Elsevier BV, 2000) Eric Deharo; Mark Loyevsky; Christy S. John; Elfride Balanza; Grace Ruiz; Victoria Muñoz; Victor R. Gordeuk
Andean high-altitude dwellers with the NFKB1 haplotype (rs230511) are protected from acute mountain sickness
(Elsevier BV, 2025) Ricardo Amaru; Javier Valencia; Edgar Teddy Quispe Soto; Emerson Cayo; Julieta Luna; Daniela Patón; Victor R. Gordeuk; Josef T. Prchal; Jihyun Song
Abstract Acute Mountain Sickness (AMS) occurs with rapid ascent to high altitudes (&gt;2,500m), where air and oxygen pressures are lower than at sea level. AMS symptoms are headache, loss of appetite, nausea, dizziness, insomnia, fatigue and chest tightness, but severe AMS can progress to cerebral edema or pulmonary edema (PMID:26294748). Hypoxia at high altitude activates inflammatory pathways in which NF-κB signaling plays a central role. Severe hypoxia (1–3% O2) induces NF-κB-driven production of inflammatory mediators, connecting hypoxia-induced stress mediated by hypoxia-inducible factors (HIFs) with NF-κB. HIFs are also involved in responses that increase pulmonary vascular permeability, pulmonary hypertension, and edema (PMIDs:11441701;3410239;18641050). HIFs increase blood-brain barrier permeability, a central feature of high-altitude cerebral edema (PMID:33856254). NFKB1 is part of NF-κB complex and modulates NF-κB activity. NFKB1 also augments activity of HIFs. In our study of evolutionary adaptation to extreme high altitude of Andean native Aymara who have higher hemoglobin than Europeans living at the same high-altitude (PMIDs: 24039843; 29100088), we reported that the evolutionary selected T allele of NFKB1 rs230511 haplotype is linked to previously unreported alternate splicing of NFKB1, including skipping exon 4, exon 5, or both exons 4 and 5. It is present in ~90% of Aymara, but it also exists at lower frequency in Europeans, Asians and Hispanics (~30%). These alternatively spliced NFKB1 transcripts result in partial or complete loss of NFKB1 protein expression. This Aymara NFKB1haplotype is associated with increased baseline expression of inflammatory and HIF-regulated genes and correlates with those Aymara having high hemoglobin. However, under inflammatory stress, it has the opposite effect: nuclear translocation of NF-kB protein is attenuated, resulting in reduced expression of inflammatory, HIF-regulated, and prothrombotic genes (PMID:39971917). Since the incidence of AMS in the Aymara population is 0.6 % (Viruez, Horiz Med [Lima] 2020; 20(3): e943), which is markedly lower than the 1.7 % observed in non-Aymara at the same altitude (Castellanos, Correo Científico Médico 2022; 26), we hypothesized that rs230511-T is also associated with a protective role for AMS in Aymara. We studied 35 Bolivian Aymara in LaPaz (altitude of 4000 meters) who relocated to lower altitudes (&lt;400 m) for 1 month to 5 years and then returned to 4000 m and developed AMS. Among 35 subjects, 10 participants- 5 women (age 29±14 years) and 5 men (age 39±8 years)- without a history of medical comorbidities (except for one having history of gout) developed AMS. The 25 subjects who did not develop AMS served as controls (7 women, age 40±14 years and 18 men, age 38±11 years). All participants were genotyped for the NFKB1(rs230511) and NOS2 (rs34913965) variants; NOS2 was included due to a potential relationship with AMS (PMID:29100088). Among the subjects who developed AMS, the allele frequencies for the Aymara-enrichedNFKB1 variant were C:0.75 and T:0.25, compared to C:0.0 and T:1.0 in the control group (p&lt;0.0001). The genotype frequencies were CC:50%, CT:50% and TT:0% in the AMS group and CC:0%, CT:0% and TT:100% in the control group (p&lt;0.0001). For the NOS2 C/T haplotype variant, analysis of 7 AMS patients revealed that allele frequencies (T-Aymara enriched allele PMID:29100088) were C:0.14 and T:0.86, compared to C:0.1 and T:0.9 in the control group (p=0.5146). The genotype frequencies were CC:0%, CT:29%, and TT:71% in the AMS group, but CC:4%, CT:12%, and TT:84% in the control group (p=0.011). We classified AMS severity as severe (4 patients admitted to the intensive care unit), moderate (2 patients hospitalized), and mild (4 patients managed at home). Two patients with severe AMS who developed both pulmonary and cerebral edema had an Aymara NFKB1 allele frequency of C: 1.0 and T: 0.0, a 100% CC genotype. Our findings suggest that the presence of the Aymara evolutionary selected NFKB1 haplotype protects from developing AMS, whereas its absence (CC genotype) increases the likelihood of development of severe AMS. The CT genotype of NOS2 variant may also provide some protective effect. Larger cohorts and functional assays are needed to validate these associations and to further explore the molecular mechanisms by which the NFKB1 and NOS2 variants contribute to protection against AMS.
Atorvastan, Apsirin and Hydorxyurea for an Effective and Low-Cost Treatment in High-Risk Polycythemia Vera
(European Medical Journal, 2022) Ricardo Amaru; Mireya Carrasco; Victor R. Gordeuk; Teddy Quispe; Silvia Mancilla; Daniela Patón; Ariel Amaru
Introduction: Polycythemia vera (PV) treatment focuses on preventing thrombotic events and delaying transformation to myelofibrosis or leukaemia. According to risk stratification, low-risk patients require therapeutic phlebotomy combined with acetylsalicylic acid, whilst the treatment of high-risk patients with PV relies on cytoreductive therapies, employing hydroxyurea (HU), ruxolitinib, or interferons. However, in low- and middle-income countries, the availability and cost of these drugs poses a challenge in treating high-risk patients, so optimising existing resources is required. Method: A prospective longitudinal study aimed to investigate the combination of atorvastatin (ATV), aspirin, and low-dose HU as a therapeutic strategy to treat PV in high-risk patients. The study evaluated the effect of statins on erythroid colony proliferation in vitro, as well as the applicability of ATV (20 mg/day), acetylsalicylic acid (100 mg/day), and hydroxiurea (500 mg/day) in high-risk patients with PV from La Paz, Bolivia, residing at 3,600 metres above sea level. Results: Simvastatin (3.5 μm) inhibited UKE-1 cell (JAK2V617F mutated) proliferation at 33%, and burstforming unit-erythroid colonies from patients with PV at 61%. Patients receiving ATV, aspirin, and low-dose HU displayed a good response and adequate tolerance to treatment (13-years follow-up). No patients experienced myelofibrosis or transformation to leukaemia, and no severe adverse events were observed. Conclusions: This accessible, effective, and low-cost therapeutic strategy could improve adherence to treatment and the overall survival of high-risk patients with PV in resource-limited countries.
Erythroid and Cardiovascular High Altitude-Selected Haplotypes in Andean Aymaras and Tibetans
(Elsevier BV, 2017) Ricardo Amaru; Jihyun Song; N. Scott Reading; Victor R. Gordeuk; Teddy Quispe; Lorna G. Moore; Rasmus Nielsen; Josef T. Prchal
Abstract Humans migrating out of Africa encountered new conditions, including living at high altitude. Tibetans and Andean Aymaras have inhabited regions of 4,000 meters or more for ~44,000 and 14,000 years respectively (Hu et al, PLoS Genet 2017, Rademaker et al, Science 2014). There is a distinct difference in erythroid phenotypes: Aymaras are polycythemic at high altitude, while most Tibetans are not. Mutations providing an advantage in highlanders will improve fitness under hypoxic conditions,including modulation of erythropoiesis through the hypoxia-inducible factor (HIF) pathway. There are few shared, naturally-selected gene regions in Aymaras and Tibetans and these have different phenotypic associations (Bigham et al, Am J Hum Biol 2013). Aymara high-altitude selected haplotypes have not been published. Tibetan EPAS 1 (encoding HIF2a protein) haplotypes in part originated from ancient Denisovans and entered the Tibetan genome through introgression (Huerta-Sanchez et al, Nature 2014). Tibetan variant prolyl hydroxylase 2 (PHD2), a negative regulator of HIFs encoded by EGLN1 gene, encodes in cis both PHD2D4E and PHD2C127S which together have increased activity in hypoxia (Lorenzo et al, Nature Genetics 2014) and, together with a Tibetan EPAS 1 haplotype, protects from high altitude polycythemia (Tashi et al, JMM 2017). We and others previously identified other Tibetans haplotypes that are not unique but are enriched in Tibetans, including a “Tibetan” haplotype of PKLR encoding liver- and red cell-specific pyruvate kinase (PK) (Simonson et al, Science 2010, and Yi et al, Science 2010). We studied Tibetan-enriched haplotypes of EGLN1, EPAS1 and PKLR in 72 Bolivian Andean Aymaras, all residing at 4,000 m, and compared them with 347 Tibetans living at altitudes of 200 m and 4,300 m (Table). We genotyped PHD2D4E and PHD2C127S variants of EGLN1 and 10 Tibetan specific single nucleotide polymorphisms (SNPs) of EPAS1, 5 Denisovan and 5 non-Denisovan, each under different linkage disequilibrium (Hu et all, PLoS Genet 2017), 7 Tibetan enriched PKLR SNPs, and searched for Aymara selected variants by whole genome sequencing. The prevalence of the Tibetan-selected EGLN1 and EPAS1 haplotypes increased with increasing altitude of residence in Tibetans, suggesting a continuous evolutionary advantage (Tashi et al, JMM 2017). Aymaras did not have the PHD2D4E haplotype, and PHD2C127S was found at lower prevalence in heterozygote form. Aymaras shared two of five non-Denisovan EPAS1 SNPs selected in Tibetans; one, rs130005507 G allele, had a similar prevalence to Tibetans, but another, rs142764723 C allele, had a lower prevalence. We report that >90% of Tibetans and ~50% of Aymaras, but only ~10% of Europeans, have the “Tibetan ” PKLR haplotype. Aymara females with homozygous PKLR haplotypes have lower hemoglobins than heterozygotes (p=0.022). Further, the PKLR transcript in reticulocytes decreases with increasing altitude and this progressive decrease is even more pronounced in the “Tibetan” haplotype. We found Aymaras' selected haplotypes encoding BRINP3, NOS2, TBX5 ; these genes are associated with cardiovascular development and function but not hypoxia sensing. They are not enriched in Tibetans. We conclude that Aymara highlanders do not have the Tibetan PHD2D4E mutation or Denisovan-like EPAS1 variants. Furthermore, they share only two of five Tibetan non- Denisovan EPAS1 variants. The absence of these variants in Aymaras supports that Tibetan and Aymara high altitude inhabitants do not have the same ancestry, that they developed different evolutionary adaptations (Bigham et al, Am J Hum Biol 2013), and that Tibetans' EGLN1 and EPAS1 mutations are unique to that part of the world. We hypothesize that decreased PK enzyme activity would be expected to increase 2,3-diphosphoglycerate (2,3-DPG) (as is shown in people with PK enzyme deficiency) and thus be beneficial to high altitude adaptation by progressively augmenting tissue oxygen delivery with increasing altitude. Based on its association with lower hemoglobin in Aymara females, the selected “Tibetan” PKLR haplotype, present in about half of Aymaras, may contribute to their hypoxic adaptation. Additional evaluation of evolutionary selected genes including PKLR, BRINP3, NOS 2, and TBX5 and their functional consequences are in progress with Aymaras living at El Alto (4,150 m), Cochabamba (2,500 m) and Santa Cruz, (416m), Bolivia. Download : Download high-res image (320KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
History of Thrombosis at High Altitude Associates With Increased Erythropoietin
(Wiley, 2025) Ricardo Amaru; Josef T. Prchal; Mireya Carrasco; Silvia Mancilla; Teddy Quispe; Julieta Luna; Juan Carlos Valencia; Daniela Patón; Victor R. Gordeuk
In Bolivian Aymara with erythrocytosis, elevated erythropoietin strongly associates with history of thrombosis. Hypoxia and iron deficiency predict elevated erythropoietin, but they do not have a direct relationship with thrombosis history. Source: Artwork by Nadia Gordeuk.
Increased Transferrin Concentrations Are Not Associated With Thrombosis in People Living at High Altitude
(2025) Ricardo Amaru; Josef T. Prchal; Tomas Ganz; Xu Zhang; Daniela Patón; Mireya Carrasco; Emma Mancilla; Victor R. Gordeuk
In individuals with extreme environmental hypoxia, we found no evidence that increased transferrin is associated with increased thrombosis history. Rather, we observed a trend to decreased thrombosis history with increased transferrin levels.
Thrombosis at High Altitude Is Not Associated with Increased Transferrin
(Elsevier BV, 2024) Ricardo Amaru; Josef T. Prchal; Daniela Patón; Mireya Carrasco; Emma Mancilla; Victor R. Gordeuk
Bolivian Andean Aymara highlanders have been living at 4000 meters for 14,000 years, and have developed evolutionary genetic adaptations to hypoxia (PMID:28448578; PMID:29100088; PMID:36980912). These include EGLN1 encoding prolyl hydroxylase 2 (PHD2), a regulator of transferrin transcription. Transferrin increases in hypoxia and iron deficiency (PMID: 9242677); contrasting reports indicate that elevated transferrin associates with thrombosis in mice but decreased thrombosis in a congenital disorder of hypoxia-sensing (PMID: 36040436; PMID: 31310728; PMID: 8281634). We analyzed clinical and laboratory data of Andean Aymara patients with High-Altitude Anemia (n=137, mean age 45 years, female gender 79%,) or High-Altitude Erythrocytosis (n=149, mean age 56 years, female gender 30%) with transferrin results in their medical records. Iron deficiency was present in 57% of anemia and 23% of erythrocytosis patients. Mean (SD) transferrin concentration was 3.08 (1.25) g/L in anemia and 3.34 (0.84) g/L in erythrocytosis patients. Thrombosis history was present in 8% of anemia and 13% of erythrocytosis patients. In logistic regression analysis in High-Altitude Anemia patients with adjustment for age and gender, iron deficiency associated with increased thrombosis history (odds ratio [OR] 6.7, P=0.030) while higher serum transferrin associated with decreased thrombosis history (OR 0.4, P=0.013). In High-Altitude Erythrocytosis patients iron deficiency associated with increased thrombosis history (OR 5.0, P=0.005), but transferrin's association with thrombosis history was not statistically significant (OR 0.8, P=0.52). In anemia and erythrocytosis patients combined, iron deficiency associated with increased thrombosis history (OR 4.6, P=0.0006) while elevated transferrin associated with reduced thrombosis history (OR 0.62, P=0.038). In individuals with extreme environmental hypoxia, we found no evidence that increasing transferrin is associated with increased thrombosis history, but rather observed a trend to decreased thrombosis history.
Tibetan Enriched PKLR Variant Is Beneficial to High Altitude Adaption By Improving Oxygen Delivery
(Elsevier BV, 2018) Jihyun Song; Virginia Abello; Ricardo Amaru; Adelina Sergueeva; Jainagul Isakova; Penelope A. Kosinski; Brigitte A. van Oirschot; Victor R. Gordeuk; Charles Kung; Richard van Wijk
Abstract Tibetans have been living at altitudes over 3500 m for ~20,000 years and have developed unique beneficial evolutionary genetic adaptions (PMID:28448578). Our previous study identified selected genetic haplotypes in two genes, EPAS1 (encoding hypoxia-inducible factor 2-alpha [HIF2-a], a transcription factor that mediates the hypoxic response), and EGLN1 (encoding prolyl hydroxylase 2 [PHD2], a principal negative regulator of HIF stability (PMID:25129147). The presence of these two haplotypes correlates with lower hemoglobin levels in Tibetans compared to other highlanders. However, the entire diverse complex of molecular mechanisms of high altitude adaptation is still largely unknown and our study showed that neither EPAS1 nor EGLN1 variants fully explain the mechanism of protection from polycythemia in Tibetans in high altitude (PMID:28233034). We found an enriched haplotype in the PKLR gene (encoding pyruvate kinase [PK] expressed only in liver and red blood cells). The PK enzyme is in the terminal portion of the glycolytic pathway, and its decreased activity leads to accumulation of proximal glycolytic intermediates, including 2,3-diphosphoglycerate (DPG) which shifts the hemoglobin dissociation curve to right (high p50) and increases oxygen release to tissues from a unit of hemoglobin. We hypothesized that Tibetan enriched PKLR variants might improve oxygen delivery to tissues and help explain the protection from polycythemia at high altitude. Genomic analyses revealed that this PKLR haplotype is enriched in Tibetans but is not unique to Tibetans. It has the highest frequency in Tibetans (89%), with a lower prevalence in Chinese and Mongolians (~77%), Kyrgyz (~60 %), Aymara (~44 %), and Colombians (~30 %) and a much lower frequency in Caucasians (11%), perhaps explaining the heterogeneity of responses to hypoxia within and among these populations. Our study of reticulocyte RNA showed that transcript levels of PKLR progressively decrease with increasing altitude in controls and even more in Tibetans with the Tibetan evolutionary selected PKLR haplotype. Tibetans with the PKLR haplotype (heterozygotes and homozygotes) have lower PKLR transcript levels than wild type Tibetans. Because of the paucity of wildtype PKLR haplotype in Tibetans and the challenges of acquiring Tibetan samples in high altitude in China, we collected samples from 125 m (Cheboksary, Chuvashia); 800 m (Bishkek, Kyrgyzstan) and 2640 m (Bogota, Colombia). PK activity, PKLR transcript levels, and ATP decreased at 2640 m compared to 800 m, while p50 increased at 2640 m. PKLR transcript levels correlated with PK activity and ATP and inversely correlated with p50. PK activities also correlated with PKLR transcript levels and ATP and inversely correlated with p50. At 2640 m, PK activity was lower and p50 levels were higher in those with the enriched PKLR haplotype. These results demonstrate that increasing altitude decreases PK activity, resulting in increasing p50 providing a molecular basis for the previously reported improvement of oxygen delivery at high altitude (PMID:17394415). To study the roles of HIFs in the regulation of PKLR gene expression, we also collected samples from Chuvash polycythemia (CP) homozygotes and Chuvash controls. CP homozygotes have a mutation in the VHL gene, a negative regulator of HIFs, that results in augmented HIF levels. CP homozygotes had lower PKLR mRNA in reticulocytes, PK activity, and PKR protein levels in red blood cells compared to controls, while their 2,3 DPG levels were higher. These data confirm that PKLR expression levels are negatively regulated by HIFs. Our findings demonstrate that individuals in high altitudes have lower PKLR transcript levels and PK activity, resulting in high 2,3DPG and p50 which shifts the hemoglobin dissociation curve to right. This decreases affinity of hemoglobin for oxygen, which improves tissue oxygen delivery and as such is another mechanism in Tibetans that protects from high altitude polycythemia. We also demonstrate that HIFs negatively regulate PKLR expression, leading to better oxygen release from hemoglobin at high altitude. Disclosures Kosinski: Agios: Employment, Equity Ownership. Kung:Agios: Employment, Equity Ownership. van Wijk:RR Mechatronics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
“What We Know and What We Do Not Know about Evolutionary Genetic Adaptation to High Altitude Hypoxia in Andean Aymaras”
(Multidisciplinary Digital Publishing Institute, 2023) Ricardo Amaru; Jihyun Song; N. Scott Reading; Victor R. Gordeuk; Josef T. Prchal
Three well-studied populations living at high altitudes are Tibetans, Andeans (Aymaras and Quechuas), and Ethiopians. Unlike Tibetans and Ethiopians who have similar hemoglobin (Hb) levels as individuals living at sea level, Aymara Hb levels increase when living at higher altitudes. Our previous whole genome study of Aymara people revealed several selected genes that are involved in cardiovascular functions, but their relationship with Hb levels was not elucidated. Here, we studied the frequencies of known evolutionary-selected variants in Tibetan and Aymara populations and their correlation with high Hb levels in Aymara. We genotyped 177 Aymaras at three different altitudes: 400 m (Santa Cruz), 4000 m (La Paz), and 5000 m (Chorolque), and correlated the results with the elevation of residence. Some of the Tibetan-selected variants also exist in Aymaras, but at a lower prevalence. Two of 10 Tibetan selected variants of EPAS1 were found (rs13005507 and rs142764723) and these variants did not correlate with Hb levels. Allele frequencies of 5 Aymara selected SNPs (heterozygous and homozygous) at 4000 m (rs11578671_BRINP3, rs34913965_NOS2, rs12448902_SH2B1, rs10744822_TBX5, and rs487105_PYGM) were higher compared to Europeans. The allelic frequencies of rs11578671_BRINP3, rs34913965_NOS2, and rs10744822_SH2B1 were significantly higher for Aymaras living at 5000 m than those at 400 m elevation. Variant rs11578671, close to the BRINP3 coding region, correlated with Hb levels in females. Variant rs34913965 (NOS2) correlated with leukocyte counts. Variants rs12448902 (SH2B1) and rs34913965 (NOS2) associated with higher platelet levels. The correlation of these SNPs with blood cell counts demonstrates that the selected genetic variants in Aymara influence hematopoiesis and cardiovascular effects.