Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 2 of 2

Publication Record

Connections

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network.
Gallego CJ, Burt A, Sundaresan AS, Ye Z, Shaw C, Crosslin DR, Crane PK, Fullerton SM, Hansen K, Carrell D, Kuivaniemi H, Derr K, de Andrade M, McCarty CA, Kitchner TE, Ragon BK, Stallings SC, Papa G, Bochenek J, Smith ME, Aufox SA, Pacheco JA, Patel V, Friesema EM, Erwin AL, Gottesman O, Gerhard GS, Ritchie M, Motulsky AG, Kullo IJ, Larson EB, Tromp G, Brilliant MH, Bottinger E, Denny JC, Roden DM, Williams MS, Jarvik GP
(2015) Am J Hum Genet 97: 512-20
MeSH Terms: Adult, Aged, Amino Acid Substitution, Child, Cohort Studies, Female, Follow-Up Studies, Genetic Variation, Genotype, Hemochromatosis, Hemochromatosis Protein, Heterozygote, Histocompatibility Antigens Class I, Homozygote, Humans, Male, Membrane Proteins, Middle Aged, Penetrance, Prognosis, United States
Show Abstract · Added March 14, 2018
Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Hemochromatosis (HFE) gene mutations and peripheral neuropathy during antiretroviral therapy.
Kallianpur AR, Hulgan T, Canter JA, Ritchie MD, Haines JL, Robbins GK, Shafer RW, Clifford DB, Haas DW
(2006) AIDS 20: 1503-13
MeSH Terms: Adolescent, Adult, Aged, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Case-Control Studies, Female, Genetic Predisposition to Disease, Genotype, HIV Infections, Hemochromatosis, Hemochromatosis Protein, Heterozygote, Histocompatibility Antigens Class I, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Peripheral Nervous System Diseases
Show Abstract · Added December 10, 2013
OBJECTIVE - Peripheral neuropathy (PN) often complicates nucleoside reverse transcriptase inhibitor (NRTI) therapy of HIV infection and may involve mitochondrial dysfunction. Since iron deficiency is associated with some types of PN, and iron is essential for mitochondrial function, we tested the hypothesis that hemochromatosis (HFE) gene mutations influence susceptibility to NRTI-induced PN.
DESIGN - Case-control study involving multicenter, AIDS Clinical Trials Group (ACTG) protocol 384 and ACTG Human DNA Repository specimens.
METHODS - Study participants were randomized to receive three- or four-drug antiretroviral therapy with didanosine (ddI) plus stavudine (d4T) or zidovudine plus lamivudine, given with efavirenz, nelfinavir, or both, with up to three years of follow-up. PN was ascertained based on signs and symptoms. HFE C282Y and H63D genotypes were determined, and associations with PN were assessed using logistic regression.
RESULTS - : Of 509 participants, 147 (29%) developed PN, 73% of whom had been randomized to receive ddI plus d4T. Among ddI/d4T-ever-treated individuals, HFE C282Y heterozygotes developed PN on ddI/d4T significantly less often than C282Y non-carriers, adjusting for age, CD4 lymphocyte count and viral load at baseline, and concomitant antiretroviral drugs [6% vs. 35%, respectively, in whites; adjusted odds ratio (OR), 0.17; 95% confidence interval (CI) 0.03-0.83; P = 0.021]. Regardless of race/ethnicity, ddI/d4T-associated PN was uncommon in C282Y heterozygotes [race-adjusted OR, 0.30; 95% CI 0.09-0.96); P = 0.042].
CONCLUSIONS - Iron-loading HFE mutations such as C282Y are associated with a decreased risk of PN during antiretroviral therapy. This finding has potential implications for the prediction and prevention of NRTI-associated PN, particularly in populations at risk of iron deficiency.
0 Communities
2 Members
0 Resources
21 MeSH Terms