Angiotensinogen T174M and M235T variants, sodium intake and hypertension among non-drinking, lean Japanese men and women.
OBJECTIVE
To examine the interaction of sodium intake with genetic variations of the angiotensinogen gene and hypertension.


METHODS
A community-based case-reference study.


METHODS
Two rural Japanese communities.


METHODS
Non-overweight and non-drinking Japanese men and women: 229 hypertensives and 229 age-, sex- and community-matched normotensives aged 32 to 83 years.


METHODS
Polymorphisms of the angiotensinogen gene detected by an allele-specific polymerase chain reaction. A priori hypothesis is individuals with 174M (threonine-to-methionine substitution) or 235T (methionine-to-threonine substitution) allelic variations may have an elevated risk of hypertension when they have a high sodium intake, estimated by 24-h urine collection and a dietary questionnaire.


RESULTS
The genotypic frequency of the haplotype including both the 174M and 235T alleles was higher among hypertensives than among normotensives (23 versus 14%, P= 0.02). The frequency of the 174M allele was specifically higher among hypertensives than normotensives (12 versus 7%, P=0.01), and the odds ratio of hypertension associated with the 174M (versus 174T) allele was 1.8 [95% confidence interval (CI) 1.1-3.0, P=0.01]. The frequency of the 235T allele did not vary between the two groups (80 versus 82%, P= 0.40). The relationship between the 174M allele and hypertension was more evident among persons who had higher urinary sodium excretion (> = 166 mmol/day) than those with lower excretion (< 166 mmol/day): odds ratio 2.5 (95% CI, 1.2-5.2), P=0.01 versus 1.5 (95% CI, 0.7-3.1), P= 0.31; P for interaction = 0.04, and this trend was primarily observed for early-onset hypertension (< 55 years at onset). A similar but nonsignificant association was observed when stratified using present and past sodium intake scores derived from questionnaires.


CONCLUSIONS
Angiotensinogen genotype may affect the development of early-onset hypertension among Japanese, particularly in those who have a high sodium intake.
Iso
H
H
Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan. fvgh5640@mb.infoweb.ne.jp
Harada
S
S
Shimamoto
T
T
Sato
S
S
Kitamura
A
A
Sankai
T
T
Tanigawa
T
T
Iida
M
M
Komachi
Y
Y
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D000808:Angiotensinogen / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000208:ethnology* / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000235:genetics; D012424:Rural Population; D012982:Sodium, Dietary / Q000008:administration & dosage* / Q000652:urine
D017931:DNA Primers; D012982:Sodium, Dietary; D000808:Angiotensinogen