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PMID |
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TITLE |
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Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins. |
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ABSTRACT |
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The aim of this study was to assess and to compare the role of HFE polymorphisms and other genetic factors in variation in iron stores. Blood samples were obtained from 3,375 adult male and female twins (age range 29-82 years) recruited from the Australian Twin Registry. There were 1,233 complete pairs (562 monozygotic and 571 dizygotic twins). Serum iron, transferrin, transferrin saturation with iron, and ferritin were measured, and the HFE C282Y and H63D genotypes were determined. The frequency of the C282Y allele was.072, and that of the H63D allele was.141. Significant sources of variation in the indices of iron status included age, sex, age-sex interaction, body-mass index, and both the C282Y and H63D genotypes. The iron, transferrin, and saturation values of CC and CY subjects differed significantly, but the ferritin values did not. After correction for age and body-mass index, 23% and 31% of the variance in iron, 66% and 49% of the variance in transferrin, 33% and 47% of the variance in transferrin saturation, and 47% and 47% of the variance in ferritin could be explained by additive genetic factors, for men and women, respectively. HFE C282Y and H63D variation accounted for <5% of the corrected phenotypic variance, except for saturation (12% in women and 5% in men). We conclude that HFE CY and HD heterozygotes differ in iron status from the CC and HH homozygotes and that serum transferrin saturation is more affected than is serum ferritin. There are highly significant effects of other as-yet-unidentified genes on iron stores, in addition to HFE genotype. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
pubmed |
2000/03/31 09:00 |
medline |
2000/06/03 09:00 |
received |
1999/00/29 |
accepted |
2000/00/31 |
aheadofprint |
2000/00/15 |
entrez |
2000/03/31 09:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Whitfield JB |
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Whitfield |
J B |
JB |
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Biochemistry Department, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. johnwhit@bioc.rpa.cs.nsw.gov.au |
Cullen LM |
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Cullen |
L M |
LM |
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Jazwinska EC |
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Jazwinska |
E C |
EC |
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Powell LW |
|
Powell |
L W |
LW |
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Heath AC |
|
Heath |
A C |
AC |
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Zhu G |
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Zhu |
G |
G |
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Duffy DL |
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Duffy |
D L |
DL |
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Martin NG |
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Martin |
N G |
NG |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 66 |
ISSUE: 4 |
TITLE: American journal of human genetics |
ISOABBREVIATION: Am. J. Hum. Genet. |
YEAR: 2000 |
MONTH: Apr |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Print |
ISSN: 0002-9297 |
ISSNTYPE: Print |
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MEDLINE JOURNAL |
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MEDLINETA: Am J Hum Genet |
COUNTRY: United States |
ISSNLINKING: 0002-9297 |
NLMUNIQUEID: 0370475 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, U.S. Gov't, P.H.S. |
Twin Study |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
Cites |
N Engl J Med. 1988 May 26;318(21):1355-62 |
3367936 |
|
Cites |
Circulation. 1999 Sep 21;100(12):1274-9 |
10491370 |
|
Cites |
Br J Haematol. 1990 Apr;74(4):525-30 |
2346731 |
|
Cites |
Int J Cancer. 1995 Jan 17;60(2):160-2 |
7829208 |
|
Cites |
Dig Dis. 1995 Jul-Aug;13(4):205-22 |
8521607 |
|
Cites |
Semin Liver Dis. 1996 Feb;16(1):65-82 |
8723325 |
|
Cites |
N Engl J Med. 1996 Dec 12;335(24):1799-805 |
8943161 |
|
Cites |
Am J Hum Genet. 1997 Jun;60(6):1439-47 |
9199565 |
|
Cites |
Circulation. 1997 Nov 18;96(10):3300-7 |
9396420 |
|
Cites |
Blood Cells Mol Dis. 1997 Aug;23(2):269-76 |
9410470 |
|
Cites |
Psychol Med. 1997 Nov;27(6):1381-96 |
9403910 |
|
Cites |
Circulation. 1998 Apr 21;97(15):1461-6 |
9576426 |
|
Cites |
Hepatology. 1998 Jun;27(6):1563-6 |
9620327 |
|
Cites |
Tissue Antigens. 1998 Sep;52(3):230-5 |
9802602 |
|
Cites |
J Hepatol. 1998 Nov;29(5):725-8 |
9833909 |
|
Cites |
Clin Chem. 1998 Dec;44(12):2429-32 |
9836708 |
|
Cites |
Gut. 1998 Dec;43(6):830-6 |
9824612 |
|
Cites |
Br J Haematol. 1998 Dec;103(3):842-5 |
9858243 |
|
Cites |
Tissue Antigens. 1998 Nov;52(5):484-8 |
9864039 |
|
Cites |
Gastroenterology. 1999 Jan;116(1):193-207 |
9869618 |
|
Cites |
Blood Cells Mol Dis. 1998 Dec;24(4):428-32 |
9851896 |
|
Cites |
Blood Cells Mol Dis. 1998 Dec;24(4):433-8 |
9851897 |
|
Cites |
Ann Genet. 1998;41(4):195-8 |
9881181 |
|
Cites |
Clin Invest Med. 1998 Dec;21(6):251-7 |
9885759 |
|
Cites |
Am J Hum Genet. 1999 Jan;64(1):259-67 |
9915965 |
|
Cites |
Gastroenterology. 1999 Feb;116(2):372-7 |
9922318 |
|
Cites |
Hum Mutat. 1999;13(2):154-9 |
10094552 |
|
Cites |
Circulation. 1999 Feb 23;99(7):852-4 |
10027804 |
|
Cites |
Blood. 1999 Apr 15;93(8):2502-5 |
10194428 |
|
Cites |
Haematologica. 1999 Mar;84(3):248-53 |
10189391 |
|
Cites |
J Hepatol. 1999 Apr;30(4):588-93 |
10207799 |
|
Cites |
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5434-9 |
10318901 |
|
Cites |
Lancet. 1999 Jun 19;353(9170):2120-3 |
10382697 |
|
Cites |
Am J Med. 1999 Jul;107(1):30-7 |
10403350 |
|
Cites |
Am J Hum Genet. 1999 Aug;65(2):483-92 |
10417291 |
|
Cites |
Nat Genet. 1999 Aug;22(4):325-6 |
10431233 |
|
Cites |
N Engl J Med. 1999 Sep 2;341(10):718-24 |
10471457 |
|
Cites |
J Gastroenterol Hepatol. 1999 Aug;14(8):745-9 |
10482424 |
|
Cites |
Circulation. 1999 Sep 21;100(12):1268-73 |
10491369 |
|
Cites |
Blood. 1990 May 1;75(9):1870-6 |
2331526 |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
AA10249 |
NIAAA NIH HHS |
United States |
AA11998 |
NIAAA NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adult |
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Age Factors |
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Alleles |
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Amino Acid Substitution |
genetics |
Australia |
genetics |
Biological Transport |
genetics |
Body Mass Index |
genetics |
Environment |
genetics |
Ethnic Groups |
genetics |
Female |
genetics |
Ferritins |
metabolism |
Gene Frequency |
metabolism |
Genetic Variation |
genetics |
Genotype |
genetics |
HLA Antigens |
genetics |
Haplotypes |
genetics |
Histocompatibility Antigens Class I |
genetics |
Humans |
genetics |
Iron |
metabolism |
Male |
metabolism |
Membrane Proteins |
metabolism |
Middle Aged |
metabolism |
Polymorphism, Genetic |
genetics |
Sex Factors |
genetics |
Statistics as Topic |
genetics |
Transferrin |
metabolism |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
HFE protein, human |
0 |
HLA Antigens |
0 |
Histocompatibility Antigens Class I |
0 |
Membrane Proteins |
0 |
Transferrin |
9007-73-2 |
Ferritins |
E1UOL152H7 |
Iron |
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OTHER ID's |
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OTHERID |
SOURCE |
PMC1288192 |
NLM |
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