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. 2025 Apr 13;17(4):e82193.
doi: 10.7759/cureus.82193. eCollection 2025 Apr.

Association of Angiotensin-Converting Enzyme (ACE) Gene Single Nucleotide Polymorphisms (SNPs) With Hypertension in Older Japanese Adults: A Cross-Sectional Study Nested Within the Nagasaki Islands Study (NaIS)

Serina Koto  1   2 , Kazuhiko Arima  1   3 , Hiroki Nakashima  1 , Ayuko Takatani  1   2 , Satoshi Mizukami  1 , Yuji Shimizu  4   5 , Mami Tamai  2 , Atsushi Kawakami  2 , Koichiro Hamada  5 , Takahiro Maeda  5 , Shin-Ya Kawashiri  6   2   7 , Yasuhiro Nagata  6 , Kiyoshi Aoyagi  1
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Association of Angiotensin-Converting Enzyme (ACE) Gene Single Nucleotide Polymorphisms (SNPs) With Hypertension in Older Japanese Adults: A Cross-Sectional Study Nested Within the Nagasaki Islands Study (NaIS)

Serina Koto et al. Cureus. .

Abstract

Aim We aimed to investigate the association between single nucleotide polymorphisms (SNPs) in the angiotensin-converting enzyme (ACE) gene and hypertension in elderly Japanese individuals. Methods This cross-sectional validation study was nested within the Nagasaki Islands Study (NaIS), involving 1,766 community-dwelling participants aged 65 years and older. Height and weight were measured. Body mass index (BMI) was calculated from height and weight, and blood pressure was measured by trained staff. Antihypertensive medication use and lifestyle factors, including alcohol consumption, smoking habits, and exercise, were assessed by interviews. The SNP (rs4309) was genotyped using fluorescent hydrolysis probes from peripheral blood mononuclear cells. Hypertension was defined as using antihypertensive medication or a systolic blood pressure of ≥140 mmHg and/or a diastolic blood pressure of ≥90 mmHg in those not on medication. Logistic regression analysis was used to calculate adjusted odds ratios (ORs) for hypertension, adjusting for potential confounders. Results Hypertension prevalence was higher in the CC/CT genotype group compared to the TT group (71.5% vs 66.4%, p=0.025). Logistic regression showed that the CC/CT genotype was independently associated with a higher likelihood of hypertension than the TT genotype (OR=1.25, 95% confidence interval (CI) 1.001-1.548) after adjusting for age, BMI, gender, alcohol consumption, smoking, and exercise. Conclusion The CC and CT genotypes of the ACE gene were independently associated with hypertension, regardless of age, BMI, gender, and lifestyle factors. These findings support a genetically informed approach to hypertension prevention.

Keywords: angiotensin-converting enzyme (ace); genotype; hypertension; nagasaki islands study; single nucleotide polymorphisms (snps).

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Conflict of interest statement

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Nagasaki University Graduate School of Biomedical Sciences Ethics Committee issued approval 14051404-20. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

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