A Gm Haplotype Study in Relation with HLA-DR in 155 Insulin-Dependent Diabetic Patients and Their Affected and Non Affected Siblings

Summary

In order to assess interaction between HLA and Gm for susceptibility to IDDM, the families of 155 IDDM probands were typed for HLA class I. II, III antigens and 16 Gm allotypes (including G2m23). Haplotypes were obtained for both systems. Individuals bearing the equivocal haplotype Gm^{3; ± 23:5*} were excluded. The frequencies of the 6 Gui haplotypes detected were comparable in IIJDM patients, sibling controls and unrelated controls. The number of Gui haplotypes was compatible with random segregation whether or not the HLA genotype was taken into account.

However, analysis of the HLA-DR allelic combinations showed are increase of the uncommon haplotype Gm^{3; …;5*} in IDDM patients bearing DR3 in the absence of DR4 (Gm^{3; …;5*} phenotype frequency 43% vs 24% in other allelic combinations, p > 0.04). When 21 diabetic and 154 non diabetic siblings of the probands were compared, the combined presence of DR3/non 4 and Gm3^{3; …;5*} was observed in 7 (33%) affected and 11 (7%) unaffected siblings (p > 0.001), conferring a relative risk of 6.4 to sib1ings who bear both markers. All DR3/non 4 positive affected siblings (7/7,) also carried Gm3^{3; …;5*} compared with 27% (11/41) of unaffected siblings (p > 0.001).

This result suggests, that in spite of the absence of segregation distortion, interaction between Cm and HLA gene products may play a role in the familial penetrance of IDDM.

Key words

IDDM - Gm - HLA - Interactive effect - Siblings