Association of a Haplotype (196Phe/532Ser) in the Interleukin‐1‐Receptor‐Associated Kinase (IRAK1) Gene With Low Radial Bone Mineral Density in Two Independent Populations
Association of a Haplotype (196Phe/532Ser) in the Interleukin‐1‐Receptor‐Associated Kinase (IRAK1) Gene With Low Radial Bone Mineral Density in Two Independent Populations
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两个独立人群中白细胞介素 1 受体相关激酶 (IRAK1) 基因中的单倍型 (196Phe/532Ser) 与低径向骨矿物质密度的关联
DOI：
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发表时间：
2003
影响因子：
6.2
通讯作者：
H. Orimo
中科院分区：
文献类型：
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作者：
R. Ishida;M. Emi;Y. Ezura;H. Iwasaki;H. Yoshida;Takao Suzuki;T. Hosoi;S. Inoue;M. Shiraki;Hiromoto Ito;H. Orimo
骨质疏松症是一种多因素的常见疾病，被认为是多种环境和遗传决定因素相互作用的结果，包括调节骨密度的因素。白介素1(IL-1)是最有效的骨吸收因子之一，而白介素1相关激酶1(IRAK1)是IL-1受体信号转导通路的重要效应者。在对来自日本不同地理区域的两个独立的绝经后妇女群体(A组：220人，T组：126人)进行的遗传学研究中，我们发现两个群体中的桡骨骨密度水平与IRAK1基因类型具有相似的相关性。编码Phe196Ser和Ser532Leu的两个氨基酸替换变异处于完全连锁不平衡状态(D‘=1.0000，R2=1.0000，χ2=192.000，p=1.2×10−43)，在受试者中发现了两种独有的单倍型(196F/532S，频率0.74；196S/532L，频率0.26)。在这两个群体中，单倍型196F/532S与桡骨骨密度降低显著相关(在队列A中：r=0.21p=0.0017；在队列T中：r=0.23p=0.011)。骨密度在196F/532S纯合子中最低，在196S/532L纯合子中最高，在杂合子中居中。在5年的随访中，加速的骨丢失也与196F/532S单倍型相关。这些结果表明，IRAK1的变异可能是绝经后骨质疏松症的一个重要决定因素，部分是通过绝经后加速骨质丢失的机制。
Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic determinants, including factors that regulate bone mineral density. Interleukin‐1 (IL‐1) is one of the most potent bone‐resorbing factors, and interleukin‐1‐associated kinase 1 (IRAK1) is an essential effector of the IL‐1 receptor signaling cascade. In genetic studies of two independent populations of postmenopausal women (cohort A: 220 individuals and cohort T: 126 individuals) from separated geographical regions of Japan, we found that radial bone mineral density levels had similar associations with IRAK1 genotypes in both populations. Two amino acid‐substituting variations in the gene, encoding Phe196Ser and Ser532Leu, were in complete linkage disequilibrium (D′ = 1.0000, r2 = 1.0000, χ2 = 192.000, p = 1.2 × 10−43), and we found two exclusive haplotypes (196F/532S, frequency 0.74; 196S/532L, frequency 0.26) of the IRAK1 gene among our test subjects. In both populations, a significant association with decreased radial bone mineral density was identified with haplotype 196F/532S (in cohort A: r = 0.21, p = 0.0017; in cohort T: r = 0.23, p = 0.011). Radial bone mineral density was lowest among 196F/532S homozygotes, highest among 196S/532L homozygotes, and intermediate among heterozygotes. Accelerated bone loss also correlated with the 196F/532S haplotype in a 5‐year follow‐up. These results suggest that variation of IRAK1 may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.
检测紧密连锁标记之间的连锁不平衡：AI-CIII 载脂蛋白基因处的 RFLP。
影响因子：
9.8
作者：
Thompson,EA;Deeb,S;Walker,D;Motulsky,AG
通讯作者：
Motulsky,AG