J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://jh.elmerpub.com

Original Article

Volume 15, Number 1, February 2026, pages 13-22

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

Figure 1. Pearson’s correlation of mean corpuscular volume vs. age in 74 HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes (r₇₄ = 0.2983; P = 0.0098).

Figure 2. Spearman’s rank correlation of mean corpuscular volume vs. daily alcohol intake in 74 HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes (r₇₄ = 0.2860; P = 0.0135).

**Table 1.** Iron Phenotypes in 74 *HFE* p.C282Y/p.H63D Compound Heterozygotes
	Screening	Post-screening evaluation	P value
SD: standard deviation.
Men (n = 37)
Mean transferrin saturation, % ± 1 SD	65 ± 13	58 ± 17	0.0692
Mean serum ferritin, µg/L ± 1 SD	529 ± 164	531 ± 170	0.9684
Women (n = 37)
Mean transferrin saturation, % ± 1 SD	59 ± 14	53 ± 12	0.0594
Mean serum ferritin, µg/L ± 1 SD	376 ± 195	367 ± 201	0.8316

Table 1. Iron Phenotypes in 74 HFE p.C282Y/p.H63D Compound Heterozygotes

Screening

Post-screening evaluation

P value

SD: standard deviation.

Men (n = 37)

Mean transferrin saturation, % ± 1 SD

65 ± 13

58 ± 17

0.0692

Mean serum ferritin, µg/L ± 1 SD

529 ± 164

531 ± 170

0.9684

Women (n = 37)

Mean transferrin saturation, % ± 1 SD

59 ± 14

53 ± 12

0.0594

Mean serum ferritin, µg/L ± 1 SD

376 ± 195

367 ± 201

0.8316

**Table 2.** *HFE* p.C282Y/p.H63D Compound Heterozygotes in Post-Screening Evaluations^a
Variable	Men (n = 37)	Women (n = 37)	P value
^aReference ranges in men and women were 0–40 and 0–31 IU/L, respectively. ^bReference ranges in men and women were 0–37 and 0–31 IU/L, respectively. ^cReference ranges in men and women were 11–51 and 7–33 IU/L, respectively. MCP: metacarpophalangeal; SD: standard deviation.
Mean age, years (SD)	57 ± 13	62 ± 12	0.0606
Mean body mass index, kg/m² (SD)	28.7 ± 5.0	28.0 ± 5.2	0.5405
Diabetes reports, % (n)	24.3 (6)	5.4 (2)	0.2611
Mean heme iron intake, mg/day (SD)	2.4 ± 1.4	1.9 ± 1.0	0.0549
Median non-heme iron intake, mg/day (range)	12.3 (4.2, 34.9)	12.2 (4.3, 43.7)	0.4822
Median supplemental iron intake, mg/day (range)	3.9 (0, 40.5)	3.9 (0, 40.5)	0.6892
Median alcohol intake, g/day (range)	5.7 (0, 60.9)	5.7 (0, 55.8)	0.7949
Swollen or tender second/third MCP joints, % (n)	5.4 (2)	5.4 (2)	∼1.0000
Mean transferrin saturation, % (SD)	58 ± 17	53 ± 12	0.1197
Mean serum ferritin, µg/L (SD)	531 ± 170	366 ± 201	0.0003
Mean hemoglobin, g/L	155 ± 8	139 ± 9	< 0.0001
Mean corpuscular volume, fL (SD)	95.5 ± 4.0	96.0 ± 4.1	0.6087
Elevated alanine aminotransferase, % (n)^a	16.2 (6)	24.3 (9)	0.5642
Elevated aspartate aminotransferase, % (n)^b	10.8 (4)	24.3 (9)	0.2210
Elevated gamma-glutamyl transpeptidase, % (n)^c	10.8 (4)	40.5 (15)	0.0068

Table 2. HFE p.C282Y/p.H63D Compound Heterozygotes in Post-Screening Evaluations^a

Variable

Men (n = 37)

Women (n = 37)

P value

^aReference ranges in men and women were 0–40 and 0–31 IU/L, respectively. ^bReference ranges in men and women were 0–37 and 0–31 IU/L, respectively. ^cReference ranges in men and women were 11–51 and 7–33 IU/L, respectively. MCP: metacarpophalangeal; SD: standard deviation.

Mean age, years (SD)

57 ± 13

62 ± 12

0.0606

Mean body mass index, kg/m² (SD)

28.7 ± 5.0

28.0 ± 5.2

0.5405

Diabetes reports, % (n)

24.3 (6)

5.4 (2)

0.2611

Mean heme iron intake, mg/day (SD)

2.4 ± 1.4

1.9 ± 1.0

0.0549

Median non-heme iron intake, mg/day (range)

12.3 (4.2, 34.9)

12.2 (4.3, 43.7)

0.4822

Median supplemental iron intake, mg/day (range)

3.9 (0, 40.5)

0.6892

Median alcohol intake, g/day (range)

5.7 (0, 60.9)

5.7 (0, 55.8)

0.7949

Swollen or tender second/third MCP joints, % (n)

5.4 (2)

∼1.0000

Mean transferrin saturation, % (SD)

58 ± 17

53 ± 12

0.1197

Mean serum ferritin, µg/L (SD)

531 ± 170

366 ± 201

0.0003

Mean hemoglobin, g/L

155 ± 8

139 ± 9

< 0.0001

Mean corpuscular volume, fL (SD)

95.5 ± 4.0

96.0 ± 4.1

0.6087

Elevated alanine aminotransferase, % (n)^a

16.2 (6)

24.3 (9)

0.5642

Elevated aspartate aminotransferase, % (n)^b

10.8 (4)

24.3 (9)

0.2210

Elevated gamma-glutamyl transpeptidase, % (n)^c

10.8 (4)

40.5 (15)

0.0068

**Table 3.** Hepatic Fibrosis Risk in 46 *HFE* p.C282Y/p.H63D Compound Heterozygotes
	Low risk, % (n)	Intermediate risk, % (n)	High risk, % (n)	P value
^aLow risk (FIB-4 < 1.3); intermediate risk (FIB-4 1.3–2.67); and high risk (FIB-4 > 2.67). ^bLow risk (APRI < 0.5); intermediate risk (APRI 0.5–1.5); and high risk (APRI > 1.5). ^cOne-way ANOVA P test. ^dUnpaired Student’s t-test (two-tailed). APRI: AST-to-platelet ratio index; FIB-4: fibrosis-4 index; MCV: mean corpuscular volume; SD: standard deviation.
FIB-4^a	56.5 (26)	32.6 (15)	10.9 (5)	-
Mean MCV, fL (SD)	95.7 ± 3.5	96.3 ± 5.6	97.0 ± 5.1	0.8204^c
APRI^b	78.3 (36)	21.7 (10)	0 (0)	-
Mean MCV, fL (SD)	96.4 ± 4.0	94.8 ± 5.5	-	0.3140^d

Table 3. Hepatic Fibrosis Risk in 46 HFE p.C282Y/p.H63D Compound Heterozygotes

Low risk, % (n)

Intermediate risk, % (n)

High risk, % (n)

P value

^aLow risk (FIB-4 < 1.3); intermediate risk (FIB-4 1.3–2.67); and high risk (FIB-4 > 2.67). ^bLow risk (APRI < 0.5); intermediate risk (APRI 0.5–1.5); and high risk (APRI > 1.5). ^cOne-way ANOVA P test. ^dUnpaired Student’s t-test (two-tailed). APRI: AST-to-platelet ratio index; FIB-4: fibrosis-4 index; MCV: mean corpuscular volume; SD: standard deviation.

FIB-4^a

56.5 (26)

32.6 (15)

10.9 (5)

Mean MCV, fL (SD)

95.7 ± 3.5

96.3 ± 5.6

97.0 ± 5.1

0.8204^c

APRI^b

78.3 (36)

21.7 (10)

0 (0)

Mean MCV, fL (SD)

96.4 ± 4.0

94.8 ± 5.5

0.3140^d

**Table 4.** Correlations of Mean Corpuscular Volume in 74 *HFE* p.C282Y/p.H63D Compound Heterozygotes
Variable	Pearson’s coefficient r	Spearman’s coefficient r	P value
^aSee Figure 1. ^bSee Figure 2.
Age, years	0.2983	-	0.0098^a
Body mass index, kg/m²	−0.2299	-	0.0488
Heme iron intake, mg/day	−0.2478	-	0.0333
Non-heme iron intake, mg/day	-	−0.0604	0.6092
Supplemental iron intake, mg/day	-	0.0742	0.5300
Alcohol intake, g/day	-	0.2860	0.0135^b
Transferrin saturation, %	0.0667	-	0.5723
Serum ferritin, µg/L	−0.0403	-	0.7296

Table 4. Correlations of Mean Corpuscular Volume in 74 HFE p.C282Y/p.H63D Compound Heterozygotes

Variable

Pearson’s coefficient r

Spearman’s coefficient r

P value

^aSee Figure 1. ^bSee Figure 2.

Age, years

0.2983

0.0098^a

Body mass index, kg/m²

−0.2299

0.0488

Heme iron intake, mg/day

−0.2478

0.0333

Non-heme iron intake, mg/day

−0.0604

0.6092

Supplemental iron intake, mg/day

0.0742

0.5300

Alcohol intake, g/day

0.2860

0.0135^b

Transferrin saturation, %

0.0667

0.5723

Serum ferritin, µg/L

−0.0403

0.7296

**Table 5.** Mean Corpuscular Volume in 74 *HFE* p.C282Y/p.H63D Compound Heterozygotes
Variable	Mean MCV, fL ± SD with variable (n)	Mean MCV, fL ± SD without variable (n)	P value
MCP: metacarpophalangeal; MCV: mean corpuscular volume; SD: standard deviation.
Male sex	95.5 ± 4.0 (37)	96.0 ± 4.1 (37)	0.6087
Diabetes reports	94.6 ± 3.3 (8)	95.8 ± 4.2 (66)	0.4045
Swollen or tender second/third MCP joints	97.0 ± 5.5 (4)	95.6 ± 4.0 (70)	0.6768

Table 5. Mean Corpuscular Volume in 74 HFE p.C282Y/p.H63D Compound Heterozygotes

Variable

Mean MCV, fL ± SD with variable (n)

Mean MCV, fL ± SD without variable (n)

P value

MCP: metacarpophalangeal; MCV: mean corpuscular volume; SD: standard deviation.

Male sex

95.5 ± 4.0 (37)

96.0 ± 4.1 (37)

0.6087

Diabetes reports

94.6 ± 3.3 (8)

95.8 ± 4.2 (66)

0.4045

Swollen or tender second/third MCP joints

97.0 ± 5.5 (4)

95.6 ± 4.0 (70)

0.6768