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The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease

The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease
The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease
Background & Aims: Celiac disease and hereditary hemochromatosis are common HLA-defined conditions in northwestern Europe. We sought to determine whether there is a genetic relationship between the 2 diseases and if hemochromatosis susceptibility gene (HFE) mutations are protective against iron deficiency in celiac disease.
Methods: Polymerase chain reaction amplification using sequence-specific primers capable of identifying the 2 HFE gene mutations (H63D and C282Y) and the HLA class I and II alleles was used to type 145 white patients with celiac disease and 187 matched controls. Hemoglobin and fasting serum iron levels in celiac patients were measured at diagnosis.
Results: HFE gene mutations, H63D or C282Y, were identified in 70 celiac patients (48.3%) and 61 controls (32.6%) (P = 0.004). The C282Y mutation was associated with HLA-A*03 and B*07 alleles in controls and with A*01, A*03, B*08, and DRB1*0301 alleles in celiac patients; the H63D mutation was associated with HLA-A*25 and DRB1*03 alleles in controls and A*29 and DRB1*03 alleles in celiac patients. At diagnosis, celiac patients with the C282Y mutation had higher mean hemoglobin and fasting serum iron levels compared with the HFE wild type (P = 0.0002 and 0.006, respectively). This was not observed with the H63D mutation.
Conclusions: In celiac disease, HFE gene mutations are common and are in linkage disequilibrium with different HLA alleles compared with controls. A disease-specific haplotype that carries C282Y and DQB1*02 is suggested. We propose that HFE gene mutations provide a survival advantage by ameliorating the iron deficiency seen in celiac patients.
0016-5085
444-449
Butterworth, Jeffrey R.
cba8fb00-0b12-40a2-83e1-a08a1b8ad87e
Cooper, Brian T.
c0e599f0-f4fd-4473-9063-9d696e89d598
Rosenberg, William M.
ac36bd93-2303-4a46-96f6-3daee7ec53b5
Purkiss, Michael
e92ef064-c42a-4b01-bba1-2edcdcf6959f
Jobson, Shirley
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Hathaway, Mark
00633054-acf7-48f8-8958-d1e7b1da2543
Briggs, David
268ab2b4-4285-46b3-8b93-3611c5689bab
Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
Wood, Gordon M.
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Adams, David H.
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Iqbal, Tariq H.
0a4ca03e-3fd1-442f-9fa2-d2e31b7fca07
Butterworth, Jeffrey R.
cba8fb00-0b12-40a2-83e1-a08a1b8ad87e
Cooper, Brian T.
c0e599f0-f4fd-4473-9063-9d696e89d598
Rosenberg, William M.
ac36bd93-2303-4a46-96f6-3daee7ec53b5
Purkiss, Michael
e92ef064-c42a-4b01-bba1-2edcdcf6959f
Jobson, Shirley
4824e801-00f7-450b-b9d5-324ea4fe1a32
Hathaway, Mark
00633054-acf7-48f8-8958-d1e7b1da2543
Briggs, David
268ab2b4-4285-46b3-8b93-3611c5689bab
Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
Wood, Gordon M.
9ca9a723-edb8-4eaa-af33-416280368e06
Adams, David H.
843ee66f-a054-443a-a138-762913d5e744
Iqbal, Tariq H.
0a4ca03e-3fd1-442f-9fa2-d2e31b7fca07

Butterworth, Jeffrey R., Cooper, Brian T., Rosenberg, William M., Purkiss, Michael, Jobson, Shirley, Hathaway, Mark, Briggs, David, Howell, W. Martin, Wood, Gordon M., Adams, David H. and Iqbal, Tariq H. (2002) The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. Gastroenterology, 123 (2), 444-449. (doi:10.1053/gast.2002.34778).

Record type: Article

Abstract

Background & Aims: Celiac disease and hereditary hemochromatosis are common HLA-defined conditions in northwestern Europe. We sought to determine whether there is a genetic relationship between the 2 diseases and if hemochromatosis susceptibility gene (HFE) mutations are protective against iron deficiency in celiac disease.
Methods: Polymerase chain reaction amplification using sequence-specific primers capable of identifying the 2 HFE gene mutations (H63D and C282Y) and the HLA class I and II alleles was used to type 145 white patients with celiac disease and 187 matched controls. Hemoglobin and fasting serum iron levels in celiac patients were measured at diagnosis.
Results: HFE gene mutations, H63D or C282Y, were identified in 70 celiac patients (48.3%) and 61 controls (32.6%) (P = 0.004). The C282Y mutation was associated with HLA-A*03 and B*07 alleles in controls and with A*01, A*03, B*08, and DRB1*0301 alleles in celiac patients; the H63D mutation was associated with HLA-A*25 and DRB1*03 alleles in controls and A*29 and DRB1*03 alleles in celiac patients. At diagnosis, celiac patients with the C282Y mutation had higher mean hemoglobin and fasting serum iron levels compared with the HFE wild type (P = 0.0002 and 0.006, respectively). This was not observed with the H63D mutation.
Conclusions: In celiac disease, HFE gene mutations are common and are in linkage disequilibrium with different HLA alleles compared with controls. A disease-specific haplotype that carries C282Y and DQB1*02 is suggested. We propose that HFE gene mutations provide a survival advantage by ameliorating the iron deficiency seen in celiac patients.

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Published date: 2002

Identifiers

Local EPrints ID: 26975
URI: http://eprints.soton.ac.uk/id/eprint/26975
ISSN: 0016-5085
PURE UUID: 25fb962f-42fb-4bd9-ae93-2aca306a11e8

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Date deposited: 25 Apr 2006
Last modified: 15 Jul 2019 19:13

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