Selected human leukocyte antigen class II polymorphisms and risk of adult glioma

Abstract

Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1*06 (OR=1.67, 95% CI=1.17–2.39) and DRB1*13 (OR=1.69, 95% CI=1.08–2.64) alleles were associated with an increased risk of glioma, while the DQB1*05 allele showed an inverse association (OR=0.63, 95% CI=0.43–0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1*06, DQB1*05, and DRB1*13 alleles in glioma susceptibility.

Non-additive and epistatic effects of HLA polymorphisms contributing to risk of adult glioma

“…Other studies detected no association between DRB1*15 and glioma risk[17,19,20]. The previously reported association between increased glioma risk and DQB1*06 [18,19,22] is consistent with our finding that DQB1*0602 (in linkage disequilibrium with DRB1*1501 ) increased glioma risk in heterozygous carriers. We posit that the method of comparing allele frequency distribution between cases and controls used in prior studies is not as well powered to detect non-additive effects, particularly in light of the possible opposing effect directions we observed in homozygous and heterozygous carriers, contributing to the inconsistent evidence in the prior literature.…”

“…Namely, our finding that HLA-B*4001 and HLA-DRB1*1302 were protective against glioma was consistent with prior observations that HLA-B*40 and HLA-DRB1*13 were enriched among the control group[17,18,21], although the association was not significant in those prior studies and the opposite direction of effect was observed in another study[22]. Although a previous GWAS found that rosacea (recently linked to glioma risk in a large Danish cohort[5]) is associated with three HLA alleles found to be in high linkage disequilibrium in our study (DRB1*0301, DQA1*0501, and DQB1*0201)[8], we did not observe these alleles to be associated with glioma risk, suggesting that the glioma-rosacea link is not likely due to shared HLA risk variants with pleiotropic effects.…”

“…Namely, our finding of the increased risk for glioma in heterozygous carriers of HLA-DRB1*1501-DQA1*0102-DQB1*0602 is consistent with studies reporting increased glioma risk associated with DRB1*15 [18,22], with the multigene haplotypes including both DRB1*15 and DQB1*06 also conferring increased glioma risk. Other studies detected no association between DRB1*15 and glioma risk[17,19,20].…”

“…Several previous studies have examined HLA with respect to glioma risk, yielding inconsistent results across both HLA class I and II genes[17–22]. However, prior analyses were generally limited in size (with the largest study involving 255 cases) and scope (selective candidate genotyping was commonly performed, resulting in a limited number of variants being interrogated).…”

HLA Polymorphisms and Risk of Glioblastoma in Koreans

“…A few studies have evaluated potential association between HLA polymorphism and risk of glioma; however, the results remain unclear (17)(18)(19)(20)(21)(22)(23)(24). Most studies used serologic methods, which resulted in only two-digit resolution of HLA genotypes (19)(20)(21)(22)(23). Also, all but one study included only western populations (18).…”