Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk

Morrison, Brittany A.; Ucisik-Akkaya, Esma; Flores, H.; Aláez, C.; Gorodezky, Clara; Dorak, M. Tevfik

doi:10.3109/08916930903567492

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…At least two studies have reported such an association; one was conducted in a Chinese population comprising 162 childhood ALL cases and 1,000 controls (15), whereas the other was conducted in a UK population, investigated the effects by gender and observed an association only in females, which is consistent with a female-specific effect of the allele DRB1*15:01, also observed in multiple sclerosis (16).…”

Section: Discussionmentioning

confidence: 58%

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Ansary

Mohammed

Hassan

et al. 2014

Molecular and Clinical Oncology

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Abstract. Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA-DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA-DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA-DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P= 0.01). HLA-DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P= 0.01) and in refractory patients compared to those who achieved remission (P= 0.02). In conclusion, the HLA-DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA-DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study. IntroductionAcute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing one quarter of all pediatric cancers worldwide (1).Over 40 years since the first associations between particular human leukocyte antigen (HLA) profiles and disease susceptibility were described, the identification of large numbers of HLA-associated diseases parallels our improved understanding of the genetic complexity of the HLA system and its extensive polymorphism. These associations involve malignant as well as autoimmune diseases, including the well-known association between HLA-B27 and ankylosing spondylitis. Over time, several hundred diseases have been reported to occur more frequently in individuals with particular HLA genotypes (2). These diseases include a broad spectrum of immune-mediated diseases involving all major organ systems, certain malignancies, infectious diseases and, more recently, adverse reactions to particular drugs (2).One of the factors that may determine whether a child develops ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of HLA genes, an association between an HLA allele and ALL may provide support for an infectious etiology (3).The biological significance of the associati...

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Section: Discussionmentioning

confidence: 58%

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Ansary

Mohammed

Hassan

et al. 2014

Molecular and Clinical Oncology

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“…Potential interactions between HLA alleles and sex have been reported for several autoimmune disorders and human malignancies (Davis and Dorak 2010; Dorak et al 1999; Morrison et al 2010). For HLA - A variants alone, evidence of sex-specific effect further points to a short sequence motif corresponding to polymorphic amino acid residues 161, 163, and 165 of the HLA-A protein product (Song et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions

Price²,

et al. 2014

Hum Genet

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Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of “missing heritability” in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

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“…In other words, only girls born to mothers with multiple sclerosis may have an increased susceptibility to childhood acute lymphoblastic leukemia. 15 It is thought that EBV infection might contribute to development of breast cancer. Serum levels of EBV viral capsid antigen IgA and nuclear antigen-1 (EBNA-1) IgA are associated with the polymorphisms of IFNG (rs2069705) and IL10 (rs1800871) genes with breast cancer susceptibility in the Asian population.…”

Section: Association With Human Diseasesmentioning

confidence: 99%

Cytokines of the Immune System

Dembić

2015

The Cytokines of the Immune System

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Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk

Cited by 24 publications

References 34 publications

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions

Cytokines of the Immune System

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