Association Of Angiotensin Ⅱ Type 2-receptor Gene Polymorphism With Essential Hypertension

Background and objective: Up to now, two angiotensin II receptor (ATR) subtypes, angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R), have been cloned. Every subtype has a lot of gene polymorphism situs that play important roles in physiological functions and pathological changes in cardiovascular system. Many studies have demonstrated that the pharmacological effects of angiotensin II mediated by AT2R are different from these by AT1R. AT2R appears to function in opposition to and in balance with AT1R. However, the AT2R gene, like the AT1R gene, also may be involved in the development of essential hypertension (EH). The molecular structure of AT2R gene is characterized by two introns and three exons, with its entire coding region in the third exon while its regulatory elements of transcription in the first intron. In vitro, the regions that transcription is higher include both intron 1 and exon 3. The A1675G polymorphism is located in intron 1 while the A3123C polymorphism in exon 3. On these backgrounds, we examined the two single nucleotide polymorphisms (SNPs) of AT2R gene and analyzed the associations between AT2R gene polymorphism and EH in the Chinese subjects. Methods 1. The detection of SNPs: The A1675G polymorphism of the AT2R gene was determined by the nested allele-specific primer polymerase chain reaction (NASP-PCR) technique while the A3123C polymorphism of AT2R gene by the single allele-specific primer polymerase chain reaction (SASP-PCR) technique. 2. The measurement of BP: The BP of right upper arm was got by auscultation with standard mercury column sphygmomanometer. The pressure corresponded by the first Korotkoff sound was considered as systolic pressure (SBP) while that by the fifth Korotkoff sound as diastolic pressure (DBP). The valuation of BP was repeated interval two minutes later and the mean of two measurements was considered as individual real BP value. Results 1. The association of AT2R gene A1675G with EH: Compared with control group, the A allele frequency of AT2R gene A1675G was increased in EH group but the difference in tow groups was no statistical significance (P>0.05). 2. The association between AT2R gene A3123C and EH: There was no significant difference in allele frequency for AT2R gene A3123C between EH group and control group in men (P>0.05); There was no remarkable difference in genotype distribution and allele frequency for AT2R gene A3123C between EH group and control group in women (P>0.05), but the genotype frequency of AT2R gene 3123AC was significantly increased in hypertensive women compared with normaltensive women (P<0.05). 3. The association of allele genotypes combination distribution of AT2R gene A1675G and A3123C with EH: There was no notable difference in allele genotypes combination of two sites of AT2R gene 1675 and 3123 SNPs between EH group and control group in men (P>0.05) but the genotypes combination of AT2R gene 3123AC and three genotypes (AA, AG, GG) of AT2R gene 1675 were remarkably increased in hypertensive women, specially genotype of AT2R gene 1675AG and 3123ACcompared with normaltensive women (P<0.05). Conclusions 1. There was no relationship of AT2R gene A1675G polymorphism with EH. 2. The 3123AC genotype of AT2R gene A3123C polymorphism was associated with EH in women. 3. The allele combination of AT2R gene A1675G and A3123C was not related to EH in men. The genotype combination of 3123AC with 1675AA, 1675AG and 1675GG was associated with EH in women. Therefore, the women who posses the combination genotype of AT2R gene 1675AG with 3123AC may be more prone to suffer from EH.