Objective: To investigate whether CA-repeat polymorphism and A1166 --> C variant in the 3n-flanking region of AT(1)R gene are in association with the genetic susceptibily to essential hypertension (EH) in Tibetans.
Methods: A case-control study was carried out. Sibpair analysis and family linkage analysis were conducted. The CA-repeat polymorphism of AT &(1) R gene was identified by polymerase chain reaction(PCR) with fluorescence labeled dCTP as substrate and by semi-automatic sequence technology. The A1166 -->C variant was detected by PCR-RFLP.
Results: Association of AT&(1)R gene locus with EH was confirmed through the case-control study in well-characterized group of 113 Tibetan EH patients and 131 normotensives(chi(2)=26.44, P<0.001). A closer examination of this gene locus found 11 alleles from Tibetan population; allele A7 (138 bp) was more frequent in both the patients and the controls. Allele A8(140 bp) was in strong positive association with genetic susceptibility to EH in Tibetans. Frequency of allele A8 was 20.5% in EH and 7.3% in normotensives. The difference of allele frequencies between the groups was significant (chi(2)=9.64, P=0.002, OR=3.46, 95% CI 1.44-8.51). Affected sibpair analysis showed chi(2)=3.85, P=0.025; family linkage analysis gave Lod score of 0.80. No association between A1166 --> C variant in AT(1)R gene and EH in Tibetans was observed (P>0.05).
Conclusion: The result suggests that CA-repeat polymorphism of AT(1)R gene be in association with EH in Tibetans, which implicates that AT(1)R gene may be in linkage disequilibrium with the causative genes of EH.