Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Adams, Paul C.; Reboussin, David M.; Barton, James C.; McLaren, Christine E.; Eckfeldt, John H.; McLaren, Gordon D.; Dawkins, Fitzroy W.; Acton, Ronald T.; Harris, Emily; Gordeuk, Victor R.; Leiendecker–Foster, Catherine; Speechley, Mark; Snively, Beverly M.; Holup, Joan; Thomson, Elizabeth J.; Sholinsky, Phyliss

doi:10.1056/nejmoa041534

Cited by 681 publications

(711 citation statements)

References 33 publications

Supporting

Mentioning

637

Contrasting

Unclassified

Order By: Relevance

“…These observations imply that normal or elevated TfSat and SF in some subjects may be insensitive or confounded measures of the availability of iron for hemoglobin synthesis. The prevalence of liver disease, usually hepatic cirrhosis, was much greater in persons with hemochromatosis phenotypes diagnosed in medical care [2,[20][21][22] than the prevalence liver-related abnormalities in the present HEIRS Study participants [6]. In the present C282Y homozygotes, separate analyses of data from women and men, showed that the prevalence of liver-related abnormalities and g-glutamyl transpeptidase were not significant predictors of mean MCV.…”

Section: Discussionmentioning

confidence: 56%

“…In the HEIRS Study, many C282Y homozygotes were recruited from Alabama, Ontario, and Oregon [6,26]. In Alabama and Ontario, ancestry reported by white persons is predominantly attributed to the British Isles [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Participants who did not select ''White or Caucasian'' to indicate their race/ethnicity were excluded, because HFE C282Y homozygosity is uncommon in blacks and other non-white racial/ethnic groups [6,32], and the mean MCV and hemoglobin of blacks are significantly lower than those of whites [33,34], There were 1,128 white men and women who attended the CE. Data from 35 participants who reported learning about the study exclusively from a family member were excluded to control for possible ascertainment bias.…”

Section: Selection Criteriamentioning

confidence: 99%

“…The Hemochromatosis and Iron Overload Screening (HEIRS) Study used TfSat and SF measurements and HFE mutation analysis to detect the C282Y and H63D alleles as initial screening of a racially and ethnically diverse sample of more than 100,000 persons ages 25 years who attended primary care clinics associated with five HEIRS Study Field Centers in North America [5,6]. HEIRS Study participants who were found to have HFE C282Y homozygosity, regardless of iron phenotype, and participants with TfSat and SF values that exceeded study thresholds, were invited to undergo a postscreening physical and laboratory evaluation that included repeat measurement of TfSat and SF, and determination of complete blood counts (CBC) and serum concentrations of hepatic enzymes and other liver-related blood tests (Clinical Examination, CE) [5].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study

McLaren

Barton²,

et al. 2007

American J Hematol

Self Cite

View full text Add to dashboard Cite

Elevated mean corpuscular volume (MCV) is common in persons with hemochromatosis associated with HFE C282Y homozygosity. We evaluated data from the subset of non-Hispanic white participants in the Hemochromatosis and Iron Overload Screening Study to determine if elevated MCV in C282Y homozygotes is related to this genotype or to serum iron measures. Regression analysis was used to model MCV and Hb from transferrin saturation (TfSat), serum ferritin (SF), mean corpuscular hemoglobin concentration, red blood cell count, age, HFE genotype, Field Center, and presence of liver-related abnormalities in C282Y homozygotes and control subjects without HFE mutations (wt/wt genotype). Mean MCV was higher in C282Y homozygotes than in HFE wt/wt controls (94.4 vs. 89.7 fL in women; 95.3 vs. 91.2 fL in men; P < 0.0001 for both). These differences were largely associated with increased mean TfSat and SF in C282Y homozygotes. Adjusted mean MCV was 92.0 fL (95% confidence interval, 91.1, 92.9) in female C282Y homozygotes and 90.9 fL (90.3, 91.5) in controls. Among women with SF in the reference range 20-200 lg/L, adjusted mean MCV was 92.9 fL, (91.7, 94.2) in C282Y homozygotes, 1.8 fL higher than in controls (P 5 0.013). The adjusted mean MCV of male C282Y homozygotes and controls was similar (P 5 0.30). Adjusted mean Hb was 0.2 g/dL higher in women with C282Y/C282Y than in controls. Greater mean MCV in C282Y homozygosity reflects increased mean TfSat and mean SF in men and women; an additional effect of genotype on MCV and Hb was detected in women. Am. J. Hematol. 82:898-905, 2007. V V C 2007 Wiley-Liss, Inc. IntroductionElevated values of mean corpuscular volume (MCV) are common in persons with hemochromatosis. In early series of hemochromatosis cases, this was attributed to hepatic cirrhosis [1], a then-current diagnostic criterion of hemochromatosis and a common sequel of severe iron overload [1,2]. In Alabama hemochromatosis probands diagnosed in medical care, mean MCV and hemoglobin concentration (Hb) were significantly greater in HFE C282Y homozygotes than in probands with other HFE genotypes or in control subjects, and 44% of all probands had prephlebotomy values of MCV greater than the upper reference limit [3]. Further, there was a significant positive association of MCV in HFE C282Y homozygotes with serum transferrin saturation (TfSat) at diagnosis and with quantities of iron removed by phlebotomy to achieve iron depletion, but not with the presence of human leukocyte antigen-A*03 [3]. In a southern California hemochromatosis screening program that evaluated persons who attended a health appraisal clinic, mean TfSat, mean serum ferritin concentration (SF), mean MCV, and mean Hb were higher than the corresponding measures in participants without common HFE mutations [4].

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Selection Criteriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study

McLaren

Barton²,

et al. 2007

American J Hematol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Siblings and other relatives of the referred subjects were screened for haemochromatosis mutations and those relatives who were found to be homozygous wild-type or heterozygous wild-type/mutant at the HFE locus served as controls. (heterozygotes for HFE mutations are not iron-overloaded and do not suffer associated morbidities [16]). The characteristics of the study population are shown in Table 1.…”

Section: Subjectsmentioning

confidence: 99%

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.Subjects and methods: Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. Results: The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.Conclusions/interpretation: Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

show abstract

Screening for Hemochromatosis

Bacon¹

2006

Arch Intern Med

View full text Add to dashboard Cite

Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Cited by 681 publications

References 33 publications

Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study

Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

Screening for Hemochromatosis

Contact Info

Product

Resources

About