title: Immunoglobulin genes implicated in glioma risk.
abstract: Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations thatIGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped theIGHGlocus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.
authors.affiliation: Department of Microbiology and Immunology; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Janardan P
authors.initials: JP
authors.lastname: Pandey
authors.affiliation: Department of Microbiology and Immunology; Medical University of South Carolina; Charleston, SC USA.
authors.forename: Navtej
authors.initials: N
authors.lastname: Kaur
authors.affiliation: Life and Health Sciences Research Institute; University of Minho; Campus de Gualtar; Braga, Portugal ; ICVS/3B's-PT Government Associate Laboratory; Campus de Gualtar, Braga, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.affiliation: Department of Oncology; Hospital de Braga; Sete Fontes-São Victor; Braga, Portugal.
authors.forename: Julia
authors.initials: J
authors.lastname: Amorim
authors.affiliation: Department of Oncology; Hospital de Braga; Sete Fontes-São Victor; Braga, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Nabico
authors.affiliation: Department of Neurosurgery; Hospital S. João; Porto, Portugal ; Faculty of Medicine; Oporto University; Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Linhares
authors.affiliation: Department of Neurosurgery; Hospital S. João; Porto, Portugal ; Faculty of Medicine; Oporto University; Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Vaz
authors.affiliation: Life and Health Sciences Research Institute; University of Minho; Campus de Gualtar; Braga, Portugal ; ICVS/3B's-PT Government Associate Laboratory; Campus de Gualtar, Braga, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Viana-Pereira
authors.affiliation: Life and Health Sciences Research Institute; University of Minho; Campus de Gualtar; Braga, Portugal ; ICVS/3B's-PT Government Associate Laboratory; Campus de Gualtar, Braga, Portugal ; Molecular Oncology Research Center; Barretos Cancer Hospital; Barretos, SP Brazil.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
keywords: GM allotypes; Glioma; HCMV; IGHG genes; astrocytoma; glioblastoma
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