# 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)

**Authors:** Serina Koto, Kazuhiko Arima, Hiroki Nakashima, Ayuko Takatani, Satoshi Mizukami, Yuji Shimizu, Mami Tamai, Atsushi Kawakami, Koichiro Hamada, Takahiro Maeda, Shin-ya Kawashiri, Yasuhiro Nagata, Kiyoshi Aoyagi

PMC · DOI: 10.7759/cureus.82193 · Cureus · 2025-04-13

## TL;DR

This study found that certain genetic variations in the ACE gene are linked to a higher risk of hypertension in older Japanese adults.

## Contribution

The study identifies a specific ACE gene SNP (rs4309) associated with hypertension in elderly Japanese individuals.

## Key findings

- The CC/CT genotype group had a higher hypertension prevalence than the TT group.
- The CC/CT genotype was independently associated with increased hypertension risk after adjusting for lifestyle and demographic factors.

## 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.

## Linked entities

- **Genes:** ACE (angiotensin I converting enzyme) [NCBI Gene 1636]

## Full-text entities

- **Genes:** AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, KL (klotho) [NCBI Gene 9365] {aka HFTC3, KLA}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, Irs2 (insulin receptor substrate 2) [NCBI Gene 384783] {aka Irs-2}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, Irs1 (insulin receptor substrate 1) [NCBI Gene 16367] {aka G972R, IRS-1}
- **Diseases:** death (MESH:D003643), Hypertension (MESH:D006973), Alzheimer's disease (MESH:D000544), hyperactivity (MESH:D006948), primary aldosteronism (OMIM:617027), systemic sclerosis (MESH:D012595), diabetic nephropathy (MESH:D003928), cardiovascular disease (MESH:D002318), Essential hypertension (MESH:D000075222), systemic lupus erythematosus (MESH:D008180), asthma (MESH:D001249), insulin resistance (MESH:D007333), obesity (MESH:D009765), renovascular hypertension (MESH:D006978), type 1 diabetes (MESH:D003922), carcinogenesis (MESH:D063646)
- **Chemicals:** salt (MESH:D012492), aldosterone (MESH:D000450), creatinine (MESH:D003404), alcohol (MESH:D000438), sodium (MESH:D012964), aspirin (MESH:D001241)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs4335, rs4362, rs7213516, rs1800764, rs4353, rs4363, rs7214530, rs4309, rs4343, rs573790, rs4461142, rs4290, rs4291, rs4344

## Full text

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## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12076255/full.md

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Source: https://tomesphere.com/paper/PMC12076255