Hegele R A, Harris S B, Hanley A J, Zinman B
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada.
Clin Genet. 1999 Jun;55(6):438-43. doi: 10.1034/j.1399-0004.1999.550607.x.
Finding the genetic determinants of intermediate quantitative traits, such as serum creatinine and urea, might aid in finding the determinants of disease phenotypes, such as renal failure, that are, in part, defined according to threshold values imposed upon such traits. We evaluated the association between common variation in the gene encoding angiotensinogen, AGT, and the serum concentrations of creatinine and urea in non-diabetic Canadian Oji-Cree. We determined genotypes of the AGT codon 235 polymorphism among 502 non-diabetic Oji-Cree. We used multivariate analysis of variance to identify significant determinants of variation in serum concentrations of creatinine and urea and of systolic and diastolic blood pressure. We found significant associations between the AGT codon 235 genotype and serum concentrations of creatinine and urea (p = 0.017 and 0.049, respectively) and systolic blood pressure (p = 0.041). Compared with subjects with the other two genotypes, homozygotes for AGT T235/T235 had significantly lower serum concentrations of creatinine and urea and significantly higher mean systolic blood pressure. The findings suggest that the AGT T235 allele is a determinant of intermediate traits related to renal function in these aboriginal Canadians.
寻找诸如血清肌酐和尿素等中间数量性状的遗传决定因素,可能有助于找到疾病表型(如肾衰竭)的决定因素,而疾病表型部分是根据对此类性状设定的阈值来定义的。我们评估了编码血管紧张素原的基因(AGT)中的常见变异与非糖尿病加拿大奥吉 - 克里人的血清肌酐和尿素浓度之间的关联。我们确定了502名非糖尿病奥吉 - 克里人中AGT密码子235多态性的基因型。我们使用多变量方差分析来确定血清肌酐和尿素浓度以及收缩压和舒张压变异的重要决定因素。我们发现AGT密码子235基因型与血清肌酐和尿素浓度(分别为p = 0.017和0.049)以及收缩压(p = 0.041)之间存在显著关联。与其他两种基因型的受试者相比,AGT T235/T235纯合子的血清肌酐和尿素浓度显著较低,平均收缩压显著较高。这些发现表明,AGT T235等位基因是这些加拿大原住民中与肾功能相关的中间性状的一个决定因素。