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Ishida, R. et al.

Association of a promoter haplotype (-1542G/-525C) in the tumor necrosis factor receptor associated factor-interacting protein gene with low bone mineral density in Japanese women.

Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic factors that regulate bone mineral density (BMD). Tumor necrosis factor receptor associated factor-interacting protein (I-TRAF) is an essential effecter of the tumor necrosis factor receptor-signaling cascade, one of the most potent bone-resorbing systems. In genetic studies of 382 Japanese adult women, we found that genotypes of two promoter variations of I-TRAF gene, -1542T/G and -525G/C, were similarly associated with radial BMD levels. Two variations were in almost complete linkage disequilibrium (D' = 0.978, r(2) = 0.917, chi(2) = 695, 2, P = 3.4 x 10(-153)), and there were two exclusive haplotypes (-1542T/-525C, frequency 0.74, and -1542G/-525G, frequency 0.24) among our test subjects. When BMD values were compared among the three haplotypic categories (-1542G/-525G homozygotes, heterozygotes, and -1542T/-525C homozygotes), BMD was lowest among -1542G/-525C homozygotes (mean +/- SD = 0.382 +/- 0.060 g/cm(2)), highest among -1542T/-525G homozygotes (0.405 +/- 0.051 g/cm(2)), and intermediate among heterozygotes (0.395 +/- 0.056 g/cm(2)) (r = 0.11, P = 0.030). The observed trend supported a codominant effect of the relevant haplotype of I-TRAF gene in determination of radial BMD. These results suggested that variation of I-TRAF might be an important determinant for postmenopausal osteoporosis.[1]

References

Association of a promoter haplotype (-1542G/-525C) in the tumor necrosis factor receptor associated factor-interacting protein gene with low bone mineral density in Japanese women. Ishida, R., Ezura, Y., Emi, M., Kajita, M., Yoshida, H., Suzuki, T., Hosoi, T., Inoue, S., Shiraki, M., Ito, H., Orimo, H. Bone (2003) [Pubmed]

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