Mean corpuscular volume in HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes: clinical and laboratory associations

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) >50% and serum ferritin (SF) >300 μg/L (men) or TS >45% and SF >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 >28 g/d men and >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.