Relationship between the M235T and G(-6)A polymorphisms of the angiotensinogen gene.
OBJECTIVE
Previous studies have reported tight linkage disequilibrium between the T235 and the A(-6) molecular variants of the angiotensinogen gene. This study was designed primarily to ascertain whether a similar relationship exists between the M235 and the G(-6) variants of the gene. We have investigated 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 hypertensive 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 subjects, 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 respectively (chi-square, P < 0.0001). The agreement for TT-AA, MT-GA, and MM-GG was 93%, 91%, and 76% respectively in white and 100%, 67% and 0% respectively 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 degree of agreement in the order of TT-AA > MT-GA > MM-GG suggests that linkage disequilibrium between the M235 and G-6 variant does not mirror that observed 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.
Onipinla
A K
AK
Blood Pressure Unit, St. George's Hospital Medical School, London, UK.
Barley
J
J
Carter
N D
ND
MacGregor
G A
GA
Sagnella
G A
GA
D000808:Angiotensinogen / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D017691:Caribbean Region / Q000208:ethnology; D016009:Chi-Square Distribution; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D006113:United Kingdom / Q000453:epidemiology; D044465:White People / Q000235:genetics*
D000808:Angiotensinogen