Mapping of a Dde I RELP of the α₂-Adrenoceptor Gene and the Correlation of Genotype with Blood Pressure in the F₂ Rats of SHR-WKY Cross

To examine a pathogenetic role of α₂-adrenoceptor (α₂-AR) in genetically hypertensive rats, we compared the α₂-AR gene of spontaneously hypertensive rats (SHR) and its normotensive control Wistar-Kyoto (WKY) rats by restriction fragment length polymorphism (RFLP) analysis and did a genetic cosegregation study. After screening with 52 restriction endonucleases (RE), an RFLP was found by digestion of the genomic DNA of SHR and WKY rat with Dde I RE and using a human platelet α₂-AR probe, the gene (ADRA2R) which is localized in chromosome 10. Restriction mapping analysis revealed that the RFLP is located in the 5′ region of the α₂-AR gene. This RFLP was used as a marker in a genetic cosegregation study to examine the correlation of genotype with blood pressure in F₂ rats of SHR and WKY rat cross. The distribution of the genotypes based on the RFLP conformed to a 1:2:1 ratio in male F₂ rats as expected for Mendelian inheritance, but not in female F₂ rats. The number of female F₂ rats with double SHR alleles was decreased about 68% from expected. Blood pressure of the male or female F₂ rats homozygous for the SHR α₂-adrenoceptor alleles was not significantly higher than the F₂ rats heterozygous or homozygous for the WKY alleles with either indirect or direct blood pressure measurement. The additional finding was that males had higher blood pressure than females. This study ruled out the cosegregation of α₂-adrenoceptor RFLP with higher blood pressure in the F₂ rats of SHR and WKY cross. However, Since the abnormality of the renal α₂-adrenoceptor in genetically hypertensive rats is one of altered regulation, and the RFLP we found is located in the 5′ region of the gene where functionally important sequences are located which regulate gene expression, this RFLP may still be of interest in genetically hypertensive rats. (Hypertens Res 1992; 15: 143-148).