HLA alleles and susceptibility to osteoporosis in men

Background: Osteoporosis (OP) is a disease of the skeleton characterized by compromised bone strength leading to an increased risk of fracture. The disease predominantly affects women because of the important pathogenic role played by gonadal steroid, however in recent decades has been demonstrated the increased prevalence of OP in men. Osteoporosis is a multifactorial disease strongly influenced by genetics factors. Studiesof twins and families with OP show that the genetic contribution to the pathogenesis of OP is responsible for 50-80% of the interindividual variability in bone mineral density (BMD). Among the susceptibility genes involved a role could be played by the HLA polymorphism. Some studies of women report an increase in HLA-B7allele in osteoporotic patients compared with controls; in particular the increaseof HLA-B7 is linked to HLA A24-B7-DR1 and HLA B7-DR15-DQ6 haplotypes. Objectives: Typing for HLA I and II genes in49 men and 81 women with OP and in 107 healthy control individuals and assess any differences in allele distribution among the three groups, in order to identify possible susceptibility genes in osteoporotic men. Methods: We selected 49 men with osteoporosis, 18 belonging to primary osteoporosis and 31 to secondary osteoporosis due to inflammatory rheumatic diseases; a group of 107 healthy control and a group of 81 women (41 with prymary OP and 40 with secondary OP) were also studied. To analyze the statistical dependence of variables in different groups we used the χ2 test with one degree of freedom, or Fisher’s exact test when necessary. Results: We observed no differences among the three groups in the frequencies of alleles of loci HLA-DRB and HLADQB. Nevertheless, valuating HLA Class I loci we observed a significant increasein the frequency of HLA-B16 in the group of males compared to controls (16% vs 6%) Pc 0,03) and in respect to the women group.(16% vs 8% Pc 0,02). Conclusions: The study of the distribution of HLA alleles in males shows an increased frequency of HLA-B16, never described in other studies. However hasn’t been demonstrated the increased frequency of HLA-B7 previously found in women with OP. The association of HLA-B7 with the OP in women, confirmed by several studies, allows us to hypothesize that this allele may be a marker of susceptibility to OP. HLA-B16 could play the same role in the male population of OP; however, being an original data, obtained on a relatively small sample, it needs to be confirmed on larger series and further studies.