Genetic screening for iron overload: No evidence of discrimination at 1 year

Identifying the subjects

The research team screened a multiracial/ethnic sample of 101,168 primary care patients, 25 years of age and older, over a 2-year period beginning in March 2001. We recruited participants in approximately equal numbers at 5 field centers, 4 in the US and 1 in Canada. We chose study sites and recruitment goals to produce a sample with about 50% non-Caucasians. A central laboratory assayed blood samples for transferrin saturation, serum ferritin, and HFE C282Y and H63D mutations. A comprehensive clinical evaluation was offered to all C282Y homozygotes and to all non-C282Y homozygotes who met study thresholds for elevated transferrin saturation and serum ferritin iron measures.¹⁷

We identified a total of 2253 such participants. Of these, 1677 (74%) participated in the clinical exam, which assessed body iron stores and attempted to distinguish between primary and secondary causes of iron overload. Clinical exam results were provided to the participants—and, if they consented, to their primary care providers. We then mailed an extended survey to all 1677 participants assessing various psychological and behavioral issues related to genetic screening and testing; 1154 responded (68.8%).

Follow-up 1 year later

One year after the clinical exam, we resurveyed these 1154 respondents and asked additional questions about any problems with employment or insurance (health, life, or disability) in the past year “related to hemochromatosis or iron overload.” Participants who had problems were contacted by telephone for follow-up questions about the nature and circumstances of the problem.

For comparison with clinical exam participants, we surveyed a stratified random sample of 939 screening participants in a similar fashion 1 year following screening. These participants were not eligible for a clinical exam but they had inconclusive screening results, indicating possible elevated risk of hereditary hemochromatosis/iron overload, such as HFE genotypes other than C282Y homozygosity, or lesser elevations of transferrin saturation or serum ferritin.¹⁸ Also surveyed at 1 year were 803 controls (469 of whom had a clinical exam and 334 who did not), who were randomly selected following the age distribution of the other participants. All controls had no known HFE genotypes associated with iron overload and had transferrin saturation and serum ferritin values below study-defined thresholds for risk of iron overload.

Results

Overall, 832 clinical exam participants (72.1%) responded among the 1154 who were surveyed 1 year after their exam. Sample characteristics are shown in TABLE 1.

Few discrimination problems were found

Twenty-four (2.8%) reported they had 1 or more problems with employment or insurance that they believed were related to hereditary hemochromatosis/iron overload. Researchers made follow-up phone contact with 17 of these (70.8%), but 7 were lost to follow-up. Only 3 of these 17 participants verified problems that were possibly related to the participation in the HEIRS Study. Among the comparison group respondents (controls and inconclusive screening results), 6 (0.5%) reported a problem with employment or insurance. However, after we made contact with 5 of the 6 respondents, we were unable to verify any of the 5 cases.

All 3 verified reports of problems came from participants who received a clinical exam based on elevated transferrin saturation and serum ferritin levels, rather than based on their HFE genotypes. There were no verified reports from any of the 153 newly identified C282Y homozygotes who responded (out of a total of 252 such participants in the HEIRS Study). Details of the 3 verified problems are shown in TABLE 2.

One person with primary iron overload was denied long-term care insurance. Two people with elevated transferrin saturation and serum ferritin levels of undetermined cause reported having problems with life insurance. One was charged an increased rate, and the second one was initially refused insurance but was later covered after a physician explained that serum iron measures had returned to normal. There were no verified reports of problems with health insurance or employment. (None of the 7 participants who reported problems but who were lost to further follow-up were newly identified C282Y homozygotes, nor did any have C282Y or H63D HFE mutations.)

TABLE 1
Characteristics of all who responded to follow-up