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Individual and joint effects of genetic polymorphisms in microRNA-machinery genes on congenital heart disease susceptibility

Part of: Basic Science

Published online by Cambridge University Press:  11 January 2021

Andrea Borghini Open the ORCID record for Andrea Borghini [Opens in a new window] ,
Cecilia Vecoli ,
Antonella Mercuri ,
Stefano Turchi  and
Maria Grazia Andreassi
Andrea Borghini*
Affiliation:
CNR Institute of Clinical Physiology, Pisa, Italy
Cecilia Vecoli
Affiliation:
CNR Institute of Clinical Physiology, Pisa, Italy
Antonella Mercuri
Affiliation:
CNR Institute of Clinical Physiology, Pisa, Italy
Stefano Turchi
Affiliation:
CNR Institute of Clinical Physiology, Pisa, Italy
Maria Grazia Andreassi
Affiliation:
CNR Institute of Clinical Physiology, Pisa, Italy
*
Author for correspondence: Dr A. Borghini, CNR Institute of Clinical Physiology, Via Moruzzi 1, Pisa 56124, Italy. Tel: 39 050 315 3204; Fax: 39 050 315 2166. E-mail: [email protected]
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Abstract

Single-nucleotide polymorphisms in miRNA-machinery genes may alter the biogenesis of miRNAs affecting disease susceptibility. In this case–control study, we aimed to evaluate the impact of three single-nucleotide polymorphisms (DICER rs1057035, DROSHA rs10719, and XPO5 rs11077) and their combined effect in a genetic risk score model on congenital heart disease (CHD) risk. A total of 639 participants was recruited, including 125 patients with CHD (65 males; age 9.2 ± 10 years) and 514 healthy controls (289 males; age 15.8 ± 18 years). Genotyping of polymorphisms in miRNA-machinery genes was performed using a TaqMan®SNP genotyping assay. A genetic risk score was calculated by summing the number of risk alleles of selected single-nucleotide polymorphisms. There was a significantly increased risk of CHD in patients with XPO5 rs11077 CC genotype as compared to AC heterozygote and AA homozygote patients (ORadjusted = 1.7; 95% CI: 1.1–2.8; p = 0.018). A clear tendency to significance was also found for DROSHA rs10719 AA genotype and CHD risk for both codominant and recessive models (ORadjusted = 1.8; 95% CI: 0.91–3.8; p = 0.09 and ORadjusted = 1.9; 95% CI: 0.92–4; p = 0.08, respectively). The resulting genetic risk score predicted a 1.73 risk for CHD per risk allele (95% CI: 1.2–2.5; p = 0.002). Subjects in the top tertile of genetic risk score were estimated to have more than three-fold increased risk of CHD compared with those in the bottom tertile (ORadjusted = 3.52; 95% CI: 1.4–9; p = 0.009). Our findings show that the genetic variants in miRNA-machinery genes might participate in the development of CHD.

Keywords

Congenital heart diseasesingle-nucleotide polymorphismDICERDROSHAXPO5
Type
Original Article
Information
Cardiology in the Young , Volume 31 , Issue 6 , June 2021 , pp. 965 - 968
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

Andrea Borghini and Cecilia Vecoli are both first authors on this review with a shared first co-authorship.

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