期刊
BONE
卷 35, 期 1, 页码 198-203出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2004.02.022
关键词
bone ALP; baboon; skeletal genetics; animal models; gender differences; variance components; osteoporosis
资金
- NCRR NIH HHS [P51 RR013986-085941, P51 RR013986-076705, P51 RR013986] Funding Source: Medline
- NHLBI NIH HHS [R01 HL54141, P01 HL28972] Funding Source: Medline
- NIAMS NIH HHS [F32 AR049694-01A1, F32 AR049694, F32 AR049694-02] Funding Source: Medline
- NIMH NIH HHS [R01 MH59490] Funding Source: Medline
While more than 77% of the people in the US with osteoporosis are women, the contributions of genotype-by-sex (GxS) and environment-by-sex interactions to sex differences in osteoporosis risk factors have not been studied. To address this issue, we conducted a statistical genetic analysis of serum concentrations of bone-specific alkaline phosphatase (Bone ALP), a highly specific marker of osteoblast function that is elevated in persons with conditions like osteoporosis characterized by excessive bone turnover or rapid bone loss. We assayed Bone ALP from 657 pedigreed baboons using a commercially available ELISA kit. Using a maximum likelihood variance decomposition approach, we treated sex as an environmental milieu in which genes influencing Bone ALP levels are expressed. We modeled the genetic covariance in Bone ALP between all relative pairs conditional on their sex so that the covariance is the product of the kinship, the genetic correlation between trait levels in the two sexes, and the genetic variances in the two sexes. Sex-specific maximum likelihood estimates (MLE) of residual heritability for Bone ALP were greater for females than for males (h(2) = 0.44 vs. h(2) = 0.26, respectively), but likelihood ratio tests revealed only a marginally significant difference in sex-specific genetic variances (P = 0.057). In contrast, the between-sex genetic correlation (rho(G) = 0.43) was significantly less than 1.0 (P = 0.037), and the difference in sex-specific environmental variances was highly significant (P = 0.00006). We report the first evidence for GxS interactions influencing variation in an osteoporosis risk factor. The diminished between-sex genetic correlation implies that different genes influence Bone ALP levels in the two sexes. The significant differences between environmental variances suggest that unmeasured factors, including those from the internal, biological environments of the two sexes, account for a greater proportion of the Bone ALP variation in males. (C) 2004 Elsevier Inc. All rights reserved.
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