A biased Gm haplotype and Gm paraprotein allotype in multiple myeloma suggests a role for the Gm system in myeloma development

Abstract

The association between a particular Gm haplotype and susceptibility to multiple myeloma (MM) is not clear. The reason is probably because no investigations have so far been carried out on the relationship between the Gm haplotype, which represents the inherited combination of IgG Gm allotypes, and the Gm allotype expressed at the IgG paraprotein (M-component), which reflects the enhanced gene expression within the haplotype in MM. We studied the incidence of Gm allotypic markers present in IgG subclasses in the serum from 52 patients with MM and in parallel with the isolated IgG paraproteins. The results showed that 84.6% of the patients were heterozygous for haplotypes Gm(a; z; n-; g;)/Gm(f; n+/n-; b1; b0; b5) and 15.3% were homozygous for Gm(f; n/n-; b1; b0; b5), while no homozygous Gm(a; z; n-; g) individuals were found among the studied patients. The incidence of these combinations in the healthy population in Serbia is 34%, 66% and lt 1%, respectively. Subjects with Gm(a; z; n-; g)/Gm(f; n+/n-; b1; b0; b5) combination are over 10 times [odds ratio (OR) = 10.69; 95% confidence interval 1.67-68] as likely to be affected by the disease as the subjects with homozygous Gm(f; n+/n-; b1; b0; b5) combination (OR = 0.35, 95% confidence interval 0.06-2.23). However, despite the Gm heterozygosity, most of the Gm(a; z; n-; g;)/Gm(f; n+/n-; b1; b0; b5) positive patients with MM (86.3%) had IgG paraprotein with the allotypic marker from the Gm(f; n+/n-; b1; b0; b5) haplotype. Together with patients homozygous for this haplotype, the relative number of patients with serum IgG paraprotein carrying allotypic marker from the Gm(f; n/n-; b1; b0; b5) haplotype was 88.5%. These results suggest that the development of an M-component could be related to a disturbance on chromosome 14q32 carrying the Gm (f; n+/n-; b1; b0; b5) set of genes.