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Background <p>Studies have confirmed a correlation between <i>angiotensin-converting enzyme 2 (ACE2</i>) gene polymorphisms and the risk of hypertension; however, its correlation with congenital heart disease (CHD)-related-pulmonary arterial hypertension (PAH) risk in neonates has not been reported.</p> Methods <p>The study enrolled 321 Han Chinese neonates, comprising 113 healthy controls and 208 patients with left-to-right shunt CHD. Among the CHD patients, 98 cases were classified as the PAH subtype [CHD PAH (+)]. Tag SNP genotyping was performed using Sanger sequencing. Associations between three <i>ACE2</i> SNPs (rs2074192, rs2285666, and rs2106809) and CHD PAH (+) neonates were assessed via sex-stratified logistic regression. Differences in circulating <i>ACE2</i> and <i>angiotensin1-7 [Ang(1–7)]</i> levels across <i>ACE2</i> haplotypes were compared using analysis of variance (ANOVA).</p> Results <p>No significant associations were observed between the three <i>ACE2</i> SNPs and susceptibility to CHD or the risk of PAH in either univariable or multivariable analyses. In females, the <i>CCT</i> haplotype showed a nominally suggestive association with CHD-PAH in both the univariable model (OR = 0.216, 95% CI: 0.047–0.740; <i>P</i> = 0.025; FDR_<i>P</i> = 0.074) and the multivariable model (OR = 0.187, 95% CI: 0.039–0.670; <i>P</i> = 0.018; FDR_<i>P</i> = 0.053). A nominal difference in circulating <i>Ang-(1–7)</i> levels was also observed across haplotypes among females, with higher levels in <i>CCT</i> haplotype carriers than in those carrying the <i>CTC</i> or <i>TCT</i> haplotypes (160.16 ± 19.24 pg/mL vs. 140.54 ± 28.40 pg/mL and 139.77 ± 29.85 pg/mL, respectively; <i>P</i> = 0.037). However, this difference did not survive FDR correction (FDR_<i>P</i> = 0.074).</p> Conclusions <p>Our study showed that there was no significant association between <i>ACE2</i> SNPs or haplotypes and the risk of CHD-PAH in neonates.</p> Trial registration <p>Our study is an observational study. According to the International Committee of Medical Journal Editors (ICMJE), purely observational studies (in which the allocation of medical interventions is not under the investigator’s discretion) do not require registration.</p>

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Association of ACE2 gene polymorphisms with risk of pulmonary arterial hypertension in neonates with congenital heart disease

  • 期刊论文

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  • 发表日期：

    2026年7月29日

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  • Youfang Chen,
  • Cuiling Wang,
  • Qingfan Lin,
  • Jin Chen,
  • Li Lin,
  • Shimu Luo,
  • Yinshuang Li,
  • Lifeng Deng

摘要

Background

Studies have confirmed a correlation between angiotensin-converting enzyme 2 (ACE2) gene polymorphisms and the risk of hypertension; however, its correlation with congenital heart disease (CHD)-related-pulmonary arterial hypertension (PAH) risk in neonates has not been reported.

Methods

The study enrolled 321 Han Chinese neonates, comprising 113 healthy controls and 208 patients with left-to-right shunt CHD. Among the CHD patients, 98 cases were classified as the PAH subtype [CHD PAH (+)]. Tag SNP genotyping was performed using Sanger sequencing. Associations between three ACE2 SNPs (rs2074192, rs2285666, and rs2106809) and CHD PAH (+) neonates were assessed via sex-stratified logistic regression. Differences in circulating ACE2 and angiotensin1-7 [Ang(1–7)] levels across ACE2 haplotypes were compared using analysis of variance (ANOVA).

Results

No significant associations were observed between the three ACE2 SNPs and susceptibility to CHD or the risk of PAH in either univariable or multivariable analyses. In females, the CCT haplotype showed a nominally suggestive association with CHD-PAH in both the univariable model (OR = 0.216, 95% CI: 0.047–0.740; P = 0.025; FDR_P = 0.074) and the multivariable model (OR = 0.187, 95% CI: 0.039–0.670; P = 0.018; FDR_P = 0.053). A nominal difference in circulating Ang-(1–7) levels was also observed across haplotypes among females, with higher levels in CCT haplotype carriers than in those carrying the CTC or TCT haplotypes (160.16 ± 19.24 pg/mL vs. 140.54 ± 28.40 pg/mL and 139.77 ± 29.85 pg/mL, respectively; P = 0.037). However, this difference did not survive FDR correction (FDR_P = 0.074).

Conclusions

Our study showed that there was no significant association between ACE2 SNPs or haplotypes and the risk of CHD-PAH in neonates.

Trial registration

Our study is an observational study. According to the International Committee of Medical Journal Editors (ICMJE), purely observational studies (in which the allocation of medical interventions is not under the investigator’s discretion) do not require registration.