Zagato L, Modica R, Florio M, Torielli L, Bihoreau M T, Bianchi G, Tripodi G
Division of Nephrology, Dialysis and Hypertension, S. Raffaele Hospital, Milan, Italy.
Hypertension. 2000 Nov;36(5):734-9. doi: 10.1161/01.hyp.36.5.734.
In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the alpha-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na(+)/H(+) exchanger A3; alpha-adducin; alpha(1B)-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of alpha-adducin as a candidate gene in both species.
在先前的一项研究中，我们采用候选基因方法，在米兰高血压大鼠和人类中均检测到α-内收蛋白基因（ADD1）存在一种多态性，该多态性与血压及肾脏钠代谢有关。在本研究中，我们对251只（米兰高血压品系×米兰正常血压品系）F2大鼠进行了全基因组搜索，使用了264个信息性标记，以进一步研究内收蛋白基因家族（Add1、Add2和Add3）的作用，并识别影响血压的新数量性状基因座（QTL）。我们还评估了两种不同血压测量方法（颈内动脉插管法和尾袖法）的影响。我们发现有证据表明，QTL影响大鼠1号染色体上通过颈内动脉测量的收缩压（直接SBP），在D1Rat121处对数优势（LOD）得分峰值为3.3，以及在Add1基因座的大鼠14号染色体上（LOD = 3.2）。在大鼠10号染色体上靠近D10Rat33处发现了一个通过尾部测量的收缩压（间接SBP）的QTL（LOD = 5.0）。所有这些QTL所确定的染色体区域在其他大鼠研究中未被检测到，并且包含可能参与血压调节的基因（Na(+)/H(+)交换体A3；α-内收蛋白；α(1B)-肾上腺素能受体）。因此，这些发现可能与人类高血压相关，同时考虑到米兰高血压大鼠与原发性高血压患者亚组之间的生化和病理生理相似性，这使得α-内收蛋白在两个物种中都被确定为候选基因。
