HLA-A∗24-B∗07-DRB1∗01 Haplotype Implicated with Genetic Disposition of Peak Bone Mass in Healthy Young Japanese Women

Abstract

HLA exhibits the most extensive polymorphism of any of the known human genes and is known as a genetic marker which allows genetic background of many diseases and physical phenomena. In this study, we, therefore, tried to investigate the regulation of HLA polymorphism and peak bone mass (PBM) in order to elucidate the genetic backgrounds of bone metabolism in young women. Subjects were 67 healthy young Japanese women (average age: 23.6 ± 2.6 years, Body Mass Index (BMI): 19.9 ± 2.0 who were randomly chosen. Allelic polymorphisms in HLA class I (HLA-A and -B) and HLA-class II (DRB1) were investigated by PCR-SSOP and PCR-SSP. Vitamin D Receptor (VDR) and Estrogen Receptor (ER) gene polymorphisms were also analyzed. Lifestyle factors, such as exercise and nutrition, were examined by questionnaire. Bone mineral density was examined using with Lunar DPX-L. Subjects who possessed HLA-B∗07 had a significantly lower PBM than those without B∗07 ( p < 0.05). All subjects were divided into 3 groups according to HLA haplotypes linked with HLA-B∗07, as follows: A∗24(+/−)B∗07(−)DRB1∗01(+/−), A∗24(+)B∗07(+)DRB1∗01(−), and A∗24(+)B∗07(+)DRB1∗01(+). There were no significant differences between these three groups in factors that affect bone metabolism, such as age, age at menarche, BMI, calcium intake, exercise habits, VDR or ER allele frequency. The HLA-A∗24-B∗07-DRB1∗01 haplotype had a significantly lower Z score in the lumbar spine compared with subjects without this haplotype ( p < 0.05). When the Z score was divided by values higher or lower than +1 or −1, all 3 subjects whose Z score was lower than −1.0 were found to have the HLA-A∗24-B∗07-DRB1∗01 haplotype. A significant association between HLA-A ∗24-B∗07-DRB1∗01 and Z score < −1 was found (Yate’s correction χ 2 = 10.82, p = 0.001, RR = 204). In conclusion, the HLA-A∗24-B∗07-DRB1∗01 haplotype can be considered a new genetic marker implicated with low PBM in healthy young Japanese women.