A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

Cruz, Eugénia; Vieira, Jorge; Almeida, Susana; Lacerda, Rosa; Gärtner, Andrea; Cardoso, Carla; Alves, Helena; Porto, Graça

doi:10.1186/1471-2350-7-16

Cited by 32 publications

(45 citation statements)

References 38 publications

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“…12 Finally, a study of C282Y homozygous hemochromatosis subjects demonstrated a significant association between the A*02 allele and a lower CD 8 þ T-lymphocyte count. 13 This association was not observed in healthy controls carrying the A*02 allele, indicating that the lower count may be related to a locus in LD with the A*02 allele. We identified one published report 14 of an association between the B*5802 allele and higher viral load in HIV-1 subtype C-infected Zambians, although the B*5801-Cw*03 haplotype was associated with lower viral load.…”

Section: Discussionmentioning

confidence: 92%

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Rhodes

Erlich

et al. 2008

Genes Immun

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The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 þ and CD4 þ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; B30%) compared to Caucasian Americans (CA; B50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-a-2a and ribavirin. We observed carriage of A*02 (RR ¼ 1.33(1.08-1.64); P ¼ 0.008), B *58 (RR ¼ 1.84(1.24-2.73); P ¼ 0.002) and DPB1*1701 (RR ¼ 1.57(1.09-2.26); P ¼ 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

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Section: Discussionmentioning

confidence: 92%

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Rhodes

Erlich

et al. 2008

Genes Immun

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“…However, further study is required to determine the linkage disequilibrium between HFE mutations and these genes. Moreover, recent studies of C282Y/C282Y patients have identified immunologic changes, such as lower CD8 T-lymphocyte numbers (Cruz et al 2006) and reduced expression of MHC class I molecules on the surface of blood mononuclear cells (de Almeida et al 2005). Finally, it was recently reported that patients infected with HCV genotype 3a had higher expression of hepatic MHC class I and HFE (Cardoso et al 2004).…”

Section: Discussionmentioning

confidence: 99%

The H63D Mutation of the Hemochromatosis Gene is Associated with Sustained Virological Response in Chronic Hepatitis C Patients Treated with Interferon-Based Therapy: A Meta-Analysis

Ren

Liu

et al. 2012

Tohoku J. Exp. Med.

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The hemochromatosis (HFE) gene encodes the HFE protein that regulates iron absorption. HFE mutations lead to the hemochromatosis disease of excessive iron absorption. HFE mutations may also influence the sustained virologic response (SVR, long-term virus suppression) in chronic hepatitis C patients treated with interferon-based antiviral therapy. We performed a meta-analysis of all English and Chinese language studies of HFE mutations and SVR in interferon-treated chronic hepatitis C patients indexed in the Medline, PubMed, Embase, and China National Knowledge Infrastructure databases to November 2011. Seven studies involving 605 patients with HFE mutations (homozygous or heterozygous mutation of C282Y, H63D or S65C) and 1279 with wild-type HFE (no mutation of C282Y, H63D or S65C for both alleles) were analyzed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the fixed-or random-effect models. HFE mutations were associated with significantly higher SVR rate (vs. wild-type: OR = 1.56, 95% CI: 1.23 -1.97, P < 0.001), indicating that mutation carriers were likely to achieve SVR in response to interferon-based antiviral therapy. Stratification analysis by HFE mutation type revealed that the H63D mutation was associated with a significantly higher SVR rate (OR = 1.60, 95% CI: 1.09 -2.34, P = 0.020), while the C282Y mutation was not (OR = 1.19, 95% CI: 0.71 -1.98, P = 0.510). Our metaanalysis results indicate that the H63D mutation in HFE is associated with a higher SVR rate in chronic hepatitis C patients treated with interferon-based antiviral therapy.

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“…Graphs show the plots of the least square straight lines, the 95 % confidence bands and the 95 % prediction bands leading to increased iron absorption is not corrected or iii) there is somehow an additional direct impact of the mutated HFE on the iNKT cell pool such as observed in CD8+ T lymphocyte populations [29]. This hypothesis could be in line with other immune cell defects consistently described in HH [21][22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 59%

“…They were all Caucasians from the north of Portugal, with confirmed homozygosity for the C282Y HFE mutation and no confounding co-morbidities. Clinical evaluation of the group of patients was previously described [21][22][23][24]. Twenty were males and 8 were females, with a mean age of 58 years old (range 39-80).…”

Section: Population Studiedmentioning

confidence: 99%

Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients

Maia¹,

Pereira²,

Melo

et al. 2014

J Clin Immunol

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A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

Cited by 32 publications

References 38 publications

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

The H63D Mutation of the Hemochromatosis Gene is Associated with Sustained Virological Response in Chronic Hepatitis C Patients Treated with Interferon-Based Therapy: A Meta-Analysis

Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients

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