Relationship between the M235T and G(-6)A polymorphisms of the angiotensinogen gene

Aims: Previous studies have reported tight linkage disequilibrium between t he T235 and the A(-6) molecular variants of the angiotensinogen gene. This study was designed primarily to ascertain whether a similar relationship ex ists between the M235 and the G(-6) variants of the gene. We have investiga ted the degree of agreement between the genotypes of the M235T and the G(-6 )A polymorphisms in two ethnic groups. Methods: Subjects were an heterogeneous group of normotensive and hypertens ive subjects of Caucasian (n = 77) and Afro-Caribbean (n = 51) origin. DNA was extracted from whole blood and was genotyped for both the M235T and G(- 6)A polymorphisms using PCR-based methods. Results: The distribution frequencies of the MM, MT, and TT genotypes were 0.39, 0.42, and 0.20 in white subjects, and 0.09, 0.17, and 0.74 in black s ubjects, respectively (chi-square, P < 0.0001). The distribution of AA, GA, and GG genotypes also differed between the two groups as follows: 0.22, 0. 48, and 0.30 in white subjects, and 0.82 and 0.18 and 0 in black subjects r espectively (chi-square, P < 0.0001). The agreement for TT-AA, MT-GA, and M M-GG was 93%, 91%, and 76% respectively in white and 100%, 67% and 0% respe ctively in black subjects. Conclusions: The results indicate ethnic differences in the distribution of both M235T and G(-6)A genotypes. The trend towards a decrease in the degre e of agreement in the order of TT-AB > MT-GA > MM-GG suggests that linkage disequilibrium between the M235 and G-6 variant does not mirror that observ ed with the T235 and A-6 variants. These observations may have significant implications regarding the associations between the G(-6)A polymorphism and hypertension. However, this needs to be further investigated.