{"doi":"10.1002/ajh.26058","title":"Loss of alpha‐globin genes in human subjects is associated with improved nitric oxide‐mediated vascular perfusion","abstract":"Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.","journal":"American Journal of Hematology","year":2020,"id":79078,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411232,"name":"Payal Shah","orcid":"0000-0001-5211-6169","position":1,"is_corresponding":false},{"id":411233,"name":"Silvie Suriany","orcid":"0000-0002-3871-723X","position":2,"is_corresponding":false},{"id":412535,"name":"Honglei Liu","orcid":null,"position":3,"is_corresponding":false},{"id":411234,"name":"Wanwara Thuptimdang","orcid":"0009-0000-3769-5967","position":4,"is_corresponding":false},{"id":411235,"name":"John Sunwoo","orcid":"0000-0003-4314-7232","position":5,"is_corresponding":false},{"id":411236,"name":"Patjanaporn Chalacheva","orcid":"0000-0002-9023-7903","position":6,"is_corresponding":false},{"id":411237,"name":"Saranya Veluswamy","orcid":"0009-0002-7965-2994","position":7,"is_corresponding":false},{"id":411238,"name":"R. Kato","orcid":"0000-0002-4442-8426","position":8,"is_corresponding":false},{"id":390158,"name":"John C. Wood","orcid":"0000-0003-0996-3439","position":9,"is_corresponding":false},{"id":411239,"name":"Jon Detterich","orcid":"0000-0002-2086-9569","position":10,"is_corresponding":false},{"id":411240,"name":"Michael C. K. Khoo","orcid":"0000-0001-7680-5989","position":11,"is_corresponding":false},{"id":390157,"name":"Thomas D. Coates","orcid":"0000-0001-9878-6029","position":12,"is_corresponding":false},{"id":411231,"name":"Christopher Denton","orcid":"0000-0003-3070-1775","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T21:50:33.748601Z","pmid":"33247606","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}