Olynyk, et al., 2004⁴⁶

Retrospective examination of 3011 randomly selected participants (age 20-79 y) from Busselton, Australia, cohort genotyped in 1998.

Available data from 1981, 1994, and 1998

HFE genotype
16 of 3011 C282YY homozygotes, 4 previously diagnosed and undergoing TP (those 4 were excluded) Serum available for 10 of 12 patients

Elevated iron measures
1981: 3 of 9
Median age: 30 y
1994: 9 of 10
Median age: 43 y
1998: 10 of 10
Median age: 47 y

SF level > 300 µg/L
1981: 5 of 10
1994: 5 of 10 (4 of 5 were same as 1981)
1998: 6 of 10

> 90 µmol/g

5 of 6 had biopsy in 1998

Possible iron overload
Men: 4 of 4 (calculated) with TS > 0.50 and SF level > 300 µg/L
Women: 2 of 6 (calculated) with TS > 0.45 and SF level > 200 µg/L

Fibrosis (6 had biopsy): 2 of 6

Cirrhosis: 1 of 6 (cirrhotic patient drank > 6 alcoholic drinks/day)

Diabetes: 1 patient at age 19 y; thought to be unrelated to HC

Arthralgia: 4 of 10

Good—potential for selective mortality bias, but effect appears to have been minimal because of reasonably complete followup of cohort (85%). Very small sample; not all patients were of the age at which disease expression would be expected (i.e., women > 50 y).

Retrospective cohort from Copenhagen Heart Study, 1976-2001; n = 9174

White persons > 99%

47% (9174 of 19,698) of original Copenhagen study sample

HFE genotype C282Y:C282Y
23 of 9174
20 still alive

TS > 0.50 in 2001
Men: 5 of 7, women: 13 of 16

SF level > 250 µg/L in 2001
Men: 6 of 7

SF level > 200 µg/L in 2001
Women: 10 of 16

Iron measure progression (1976-2001)

Mean TS
Women:
Mean age, 25 y: 0.50
Mean age, 85 y: 0.70
Men:
Mean age, 35 y: 0.70
Mean age, 80 y: 0.80

Mean SF level
Women:
Mean age, 25 y: 120 µg/L
Mean age, 85 y: 500 µg/L
Men:
Mean age, 35 y: 800 µg/L
Mean age, 80 y: 400 µg/L

Possible iron overload
Men: TS > 0.50, SF level > 300 µg/L, and CE: 5 of 7 (calculated)
Women: TS > -0.45, SF level > 200 µg/L, and CE: 9 of 16 (calculated)

Liver biopsies not done

Diabetes: 1 of 23 (4%)

Liver disease: 0 of 23 (0%) (Defined by AST level > 50 U/L; alkaline phosphatase level > 275 U/L; coagulation tests <70%; bilirubin level > 17)

Clinical work-ups in 2001 for liver disease, hypogonadism, cardiomyopathy: 0 of 23

Work-up for arthralgias: 2 of 23

Subclinical HC: 1 of 23

Fair—results may be compromised by selective mortality bias due to large attrition of the cohort. No liver biopsies to confirm disease expression or iron overload.