Agarwal Anupam, Williams Gordon H, Fisher Naomi D L
Harvard Medical School and Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.
Trends Endocrinol Metab. 2005 Apr;16(3):127-33. doi: 10.1016/j.tem.2005.02.009.
Hypertension is a complex genetic disorder caused by interplay between several "risk" genes and environmental factors (genetic heritability approximately 30%). Most genetic studies of hypertension use a candidate gene approach and two conclusions have been made: there is no association or linkage with the genes studied, or the hypertension phenotype is heterogeneous and subgroups with hypertension related to certain polymorphisms cannot be identified because of background noise. Studies using intermediate phenotypes suggest the latter is most likely. Another problem is the reliability of gene structure assessment: usually only one or two gene polymorphisms are assessed. The use of intermediate phenotypes and dense mapping of candidate genes would provide a better approach for identifying genotype-phenotype correlations, which might enable the use of genotypes to identify more-specific therapeutic and preventative measures for hypertensives.
高血压是一种复杂的遗传性疾病,由多个“风险”基因与环境因素相互作用所致(遗传度约为30%)。大多数高血压基因研究采用候选基因法,得出了两个结论:所研究的基因与高血压无关联或连锁关系;或者高血压表型具有异质性,由于背景噪声,无法识别与某些多态性相关的高血压亚组。使用中间表型的研究表明,后一种情况最有可能。另一个问题是基因结构评估的可靠性:通常仅评估一两个基因多态性。使用中间表型和对候选基因进行密集定位将为识别基因型-表型相关性提供更好的方法,这可能有助于利用基因型为高血压患者确定更具特异性的治疗和预防措施。