# Mean Corpuscular Volume in HFE p.C282Y/p.H63D Compound Heterozygotes With High Iron Phenotypes: Clinical and Laboratory Associations

## TL;DR

This study finds that higher age and alcohol intake are linked to increased mean corpuscular volume in people with a specific genetic mutation causing high iron levels.

## Contribution

The study identifies specific clinical associations of mean corpuscular volume in HFE compound heterozygotes with high iron phenotypes.

## Key findings

- Mean corpuscular volume (MCV) is positively correlated with age and daily alcohol intake in HFE compound heterozygotes.
- MCV was not significantly associated with transferrin saturation, serum ferritin, or diabetes in these individuals.
- Participants with heavy alcohol intake had significantly higher MCV compared to those without.

## Abstract

The aim of this study was to define the relationships between mean corpuscular volume (MCV) and 12 clinical and laboratory variables in HFE p.C282Y (rs1800562)/p.H63D (rs1799945) compound heterozygotes.

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/day in men and > 14 g/day in women. We determined associations of MCV with the following clinical and laboratory variables: age, sex, body mass index (BMI), diabetes, daily intakes of heme, non-heme, and supplemental iron, daily intakes of alcohol, swollen or tender second/third metacarpophalangeal (MCP) joints, reports of therapeutic phlebotomy, TS, and SF.

There were 74 participants (37 men, 37 women) of mean age 59 ± 12 (SD) years. 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 BMI (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 fL and 95.0 ± 3.9 fL, 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 second/third MCP joints, reports of therapeutic phlebotomy, TS, or SF.

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.