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The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease.
Gastroenterology. 2002 Aug; 123(2):444-9.G

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.

Authors+Show Affiliations

Gastroenterology Unit, City Hospital, Birmingham, England. j.r.butterworth@btinternet.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12145797

Citation

Butterworth, Jeffrey R., et al. "The Role of Hemochromatosis Susceptibility Gene Mutations in Protecting Against Iron Deficiency in Celiac Disease." Gastroenterology, vol. 123, no. 2, 2002, pp. 444-9.
Butterworth JR, Cooper BT, Rosenberg WM, et al. The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. Gastroenterology. 2002;123(2):444-9.
Butterworth, J. R., Cooper, B. T., Rosenberg, W. M., Purkiss, M., Jobson, S., Hathaway, M., Briggs, D., Howell, W. M., Wood, G. M., Adams, D. H., & Iqbal, T. H. (2002). The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. Gastroenterology, 123(2), 444-9.
Butterworth JR, et al. The Role of Hemochromatosis Susceptibility Gene Mutations in Protecting Against Iron Deficiency in Celiac Disease. Gastroenterology. 2002;123(2):444-9. PubMed PMID: 12145797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. AU - Butterworth,Jeffrey R, AU - Cooper,Brian T, AU - Rosenberg,William M C, AU - Purkiss,Michael, AU - Jobson,Shirley, AU - Hathaway,Mark, AU - Briggs,David, AU - Howell,W Martin, AU - Wood,Gordon M, AU - Adams,David H, AU - Iqbal,Tariq H, PY - 2002/7/30/pubmed PY - 2002/8/17/medline PY - 2002/7/30/entrez SP - 444 EP - 9 JF - Gastroenterology JO - Gastroenterology VL - 123 IS - 2 N2 - 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. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/12145797/The_role_of_hemochromatosis_susceptibility_gene_mutations_in_protecting_against_iron_deficiency_in_celiac_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016508502001221 DB - PRIME DP - Unbound Medicine ER -