Nakayama T, Soma M, Kanmatsuse K, Kokubun S
Division of Receptor Biology, Advanced Medical Research Center, Nihon University School of Medicine, Ooyaguchi-kamimachi, Tokyo, Japan.
J Hum Hypertens. 2004 Nov;18(11):823-8. doi: 10.1038/sj.jhh.1001740.
Essential hypertension (EH) is thought to be a polygenic disease. Several candidate genes of this disease have been investigated in studies using polymorphic genetic markers, but some studies have failed to show any association of EH with these genes. In this experiment, we used microsatellite markers on chromosome 1, and performed an association study between EH and control subjects. Genomic DNA was amplified with fluorescently labelled primers from the Applied Biosystems PRISM linkage mapping set HD-5 comprising 63 highly polymorphic microsatellite markers with an average spacing of 4.5 cM. We isolated three loci showing significant differences: D1S507, D1S2713 and D1S2842. The P-values of the allele with the greatest post hoc contributions in D1S507, D1S2713 and D1S2842 were 0.0008, 0.0062 and 0.0084, respectively. All these values were significant after Bonferroni correction. Furthermore, we found that the three microsatellite alleles were associated with the levels of systolic blood pressure. These data suggest that there are at least the three susceptibility loci for EH on chromosome 1, and that a case-control study using microsatellite markers on genomewide basis is a useful method for isolating the susceptibility loci of multifactorial disorders.
原发性高血压(EH)被认为是一种多基因疾病。在使用多态性遗传标记的研究中,已经对该疾病的几个候选基因进行了研究,但一些研究未能显示出EH与这些基因之间的任何关联。在本实验中,我们使用了1号染色体上的微卫星标记,并对EH患者和对照受试者进行了关联研究。基因组DNA用来自应用生物系统公司PRISM连锁图谱集HD-5的荧光标记引物进行扩增,该图谱集包含63个高度多态性的微卫星标记,平均间距为4.5厘摩。我们分离出三个显示出显著差异的位点:D1S507、D1S2713和D1S2842。D1S507、D1S2713和D1S2842中事后贡献最大的等位基因的P值分别为0.0008、0.0062和0.0084。经过Bonferroni校正后,所有这些值均具有显著性。此外,我们发现这三个微卫星等位基因与收缩压水平相关。这些数据表明,1号染色体上至少存在三个EH易感位点,并且基于全基因组使用微卫星标记进行病例对照研究是分离多因素疾病易感位点的一种有用方法。