{"doi":"10.1101/2025.10.10.25337747","title":"Mean corpuscular volume in <i>HFE</i> p.C282Y/p.H63D compound heterozygotes with high iron phenotypes: clinical and laboratory associations","abstract":"Abstract Background Variables that influence mean corpuscular volume (MCV) in HFE p.C282Y (rs1800562)/p.H63D (rs1799945) compound heterozygotes are inadequately defined. Methods We retrospectively studied self-reported non-Hispanic white adult compound heterozygotes with transferrin saturation (TS) &gt;50% and serum ferritin (SF) &gt;300 μg/L (men) or TS &gt;45% and SF &gt;200 μg/L (women) who participated in primary care-based screening. In post-screening evaluations, we excluded participants with anemia, pregnancy, or medication use that increases MCV. We defined heavy alcohol intake as &gt;28 g/d men and &gt;14 g/d women. We determined associations of MCV with 11 clinical and laboratory variables. Results There were 74 participants (37 men, 37 women) of mean age 59±12 (SD) y. Mean screening TS and SF were 65±13% and 529±169 µg/L (men) and 59±14% and 376±195 µg/L (women). Post-screening values did not differ significantly. Mean MCV was 95.7±4.0 fL. There was a negative correlation of MCV with body mass index (p=0.0488) and positive correlations of MCV with age (p=0.0098), daily heme iron intake (p=0.0333), and daily alcohol intake (p=0.0113). Mean MCVs of 19 participants with and 55 without heavy alcohol intake were 97.8±3.8 g/d and 95.0±3.9 g/d, respectively; p=0.0074). Linear regression on MCV confirmed positive associations with age (p=0.0064) and daily alcohol intake (p=0.0151). MCV was not significantly associated with sex, diabetes, daily intakes of non-heme and supplemental iron, swollen or tender 2nd/3rd metacarpophalangeal joints, TS, or SF. Conclusion MCV in HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes is positively associated with age and daily alcohol intake, after adjustment for other variables.","journal":"medRxiv","year":2025,"id":577785,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9405,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1416214,"name":"J. Clayborn Barton","orcid":"0000-0002-2646-4466","position":2,"is_corresponding":false},{"id":1416215,"name":"Ronald T. Acton","orcid":"0000-0002-8586-6887","position":4,"is_corresponding":false},{"id":456254,"name":"James C. Barton","orcid":"0000-0003-2876-8276","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:58:16.148027Z","pmid":null,"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":[]}