Foroud T, Ichikawa S, Koller D, Lai D, Curry L, Xuei X, Edenberg H J, Hui S, Peacock M, Econs M J
Indiana University School of Medicine, Health Information and Translational Sciences Building, Indianapolis, IN 46202-3002, USA.
Osteoporos Int. 2008 May;19(5):637-43. doi: 10.1007/s00198-007-0484-z. Epub 2007 Oct 2.
Animal studies suggest that arachidonate 5-lipoxygenase (encoded by ALOX5) may be a genetic determinant of bone mineral density. We tested this hypothesis in a sample of healthy men and women and did not find consistent evidence for an association between variation in this gene and either lumbar spine or femoral neck BMD.
Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. A recent mouse study implicated ALOX5, which encodes arachidonate 5-lipoxygenase, as a contributing factor to areal BMD (aBMD).
Fifteen single nucleotide polymorphisms (SNPs) distributed throughout ALOX5 were genotyped in three healthy groups: 1,688 European American, premenopausal sisters, 512 African American premenopausal sisters and 715 European American brothers. Statistical analyses were performed in the three groups to test for association between these SNPs and femoral neck and lumbar spine aBMD.
Significant (p < or = 0.05) evidence of association was observed with three of the SNPs. However, despite the linkage disequilibrium between SNPs, adjacent SNPs did not provide statistical evidence of association in any of the three study groups.
These data do not provide consistent evidence of association between genomic variation in ALOX5 and clinical variability in aBMD in healthy subjects.
动物研究表明,花生四烯酸5-脂氧合酶(由ALOX5编码)可能是骨密度的遗传决定因素。我们在一组健康男性和女性样本中检验了这一假设,未发现该基因变异与腰椎或股骨颈骨密度之间存在关联的一致证据。
健康成年人骨密度(BMD)的表型变异受遗传和环境因素影响。最近一项小鼠研究表明,编码花生四烯酸5-脂氧合酶的ALOX5是影响面积骨密度(aBMD)的一个因素。
在三个健康组中对分布于ALOX5的15个单核苷酸多态性(SNP)进行基因分型:1688名欧美绝经前姐妹、512名非裔美国绝经前姐妹和715名欧美兄弟。在这三组中进行统计分析,以检验这些SNP与股骨颈和腰椎aBMD之间的关联。
观察到三个SNP有显著(p≤0.05)的关联证据。然而,尽管SNP之间存在连锁不平衡,但在三个研究组中的任何一组中,相邻的SNP都未提供关联的统计证据。
这些数据未提供ALOX5基因变异与健康受试者aBMD临床变异性之间存在关联的一致证据。