Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

Hammer, Christian; Begemann, Martin; McLaren, Paul J.; Bartha, István; Michel, Angelika; Klose, Beate; Schmitt, Corinna; Waterboer, Tim; Pawlita, Michael; Schulz, Thomas F.; Ehrenreich, Hannelore; Fellay, Jacques

doi:10.1016/j.ajhg.2015.09.008

Cited by 63 publications

(103 citation statements)

References 29 publications

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“…This was mapped to the 6q23 locus, as seen in a European sample study [14,[25][26][27]. However, LD patterns at this genomic region seem different between populations of different race (European and African), origin [26,[28][29][30][31]. Using such findings, insights can be gained from populations of different race, replicate and refine genetic association signals [25,26,28].…”

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

“…Common variant within these three blocks had been shown to account for levels of fetal cell (FC) counts. This was mapped to the 6q23 locus, as seen in a European sample study [14,[25][26][27]. However, LD patterns at this genomic region seem different between populations of different race (European and African), origin [26,[28][29][30][31].…”

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

“…However, LD patterns at this genomic region seem different between populations of different race (European and African), origin [26,[28][29][30][31]. Using such findings, insights can be gained from populations of different race, replicate and refine genetic association signals [25,26,28]. This strategy was instrumental, for the identification of an additional SNP (rs4895441) with good predictive power for pain crisis combined with acute chest syndrome (ACS) rates in SCD [25].…”

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

“…This strategy was instrumental, for the identification of an additional SNP (rs4895441) with good predictive power for pain crisis combined with acute chest syndrome (ACS) rates in SCD [25]. The MYB gene is well studied for its role in hematopoiesis; however, HBS1L is a poorly characterized gene with yet unknown biological functions [26,28,31]. The mechanism on how the various SNPs influences HbF, remain largely unclear [19].…”

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

“…Some other study on the AI haplotype, genetic association protocol [25,26] was used to pinpoint HbF variant (rs4671393) in an intron of the BCLIIA gene (B-cell lymphoma/leukemia IIA), a gene expressed in erythrocyte precursors and implicated in lymphoid malignancies [15,26,27], have the strongest effect bearing, its importance in the control switching of HbF to HbA. Further AI haplotype mapping had long revealed three other single nucleotide polymorphisms (SNPs) (rs28384513, rs9399137 and rs4895441) located in the intergenic region 5' to HBS1L and the MYB (family of transcription factors operational e.g.…”

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

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Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management

Alli¹,

Okoh²

2016

Hereditary Genet

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Sickle cell disease (SCD) is a genetic disease of hemoglobin (Hb) that occurs due to a non-conservative substitution of a polar glutamate (Glu) by non-polar valine (Val) in an invariant region, of hemoglobin β chain-subunit. This change distorts the normal Hb folding resulting in a sticky patch on the surface of the β-chains and associated complications. Nigeria has the largest burden of SCD globally with an estimated 150,000 new born affected annually.This review is aimed at analyzing the phytomedicines use in Nigeria to ameliorate the crisis associated with SCD and present probable target genetic loci/pathways that this phytomedicines could act upon for effective and enhanced management of SCD in a resource poor environment.Nucleation is essential in polymerization of Hb and phyto-medicine has been reported to inhibit this pathway. Different loci of genetic variation identified as modulator of SCD phenotype include nucleotide motifs within the β-globin gene cluster and distal genes located on different chromosomes. Fetal hemoglobin (HbF) is equally an important variable and modulator of the clinical features of SCD. Phytomedicine used in the management of SCD ameliorates oxidative stress and modulates cytokines that contributes to SCD complications. Here, we propose the use of phyto-medicine as key component for genetic modification, by twinkling, some transcription effectors/gene modulator such as B-cell lymphoma/leukemia 11A (BCL11A), or an erythroid specific transcription factor (KLF1), which are part of factors mediating HbF gene silencing.

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Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

Section: Scd Phenotype and Fetal Hemoglobin (Hbf)mentioning

confidence: 99%

See 3 more Smart Citations

Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management

Alli¹,

Okoh²

2016

Hereditary Genet

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The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

Hoseinnezhad,

Soltani,

Ziarati

et al. 2024

Clinical Laboratory Analysis

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BackgroundThe COVID‐19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID‐19 outcomes.MethodsIn this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID‐19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID‐19 incidence and severity.ResultsOur review provides insights into the immunological mechanisms involving HLA‐mediated responses to COVID‐19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA‐A02, may confer a lower risk of COVID‐19, while others, like HLA‐C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations.ConclusionConsidering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID‐19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.

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The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.

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Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

Cited by 63 publications

References 29 publications

Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management

Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management

The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

The impact of HLA polymorphism on herpesvirus infection and disease

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