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Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population

OBJECTIVE: To explore the relationship between angiotensin-converting enzyme 2 (ACE2) genetic variants and gestational diabetes mellitus (GDM) in a southern Chinese population. METHODS: Potential functional variants (rs2106809, rs6632677, and rs2074192) of ACE2 were selected and genotyped in 566 GDM...

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Autores principales: Huang, Gongchen, Liang, Qiulian, Wang, Yukun, Qin, Linyuan, Yang, Haili, Lin, Lin, Yu, Xiangyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752565/
https://www.ncbi.nlm.nih.gov/pubmed/36531495
http://dx.doi.org/10.3389/fendo.2022.1052906
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author Huang, Gongchen
Liang, Qiulian
Wang, Yukun
Qin, Linyuan
Yang, Haili
Lin, Lin
Yu, Xiangyuan
author_facet Huang, Gongchen
Liang, Qiulian
Wang, Yukun
Qin, Linyuan
Yang, Haili
Lin, Lin
Yu, Xiangyuan
author_sort Huang, Gongchen
collection PubMed
description OBJECTIVE: To explore the relationship between angiotensin-converting enzyme 2 (ACE2) genetic variants and gestational diabetes mellitus (GDM) in a southern Chinese population. METHODS: Potential functional variants (rs2106809, rs6632677, and rs2074192) of ACE2 were selected and genotyped in 566 GDM patients and 710 normal pregnaõncies in Guilin, China. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between genetic variant and GDM risk, and then the false positive report probability, multifactor dimensional reduction (MDR), and bioinformatics tools were used to confirm the significant association in the study. RESULTS: After adjusting for age and prepregnancy body mass index, logistic regression analysis showed that ACE2 rs6632677 was significantly associated with a decreased risk of GDM (CC vs. GG: adjusted OR = 0.09, 95% CI: 0.01 – 0.71, P = .023; GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46 – 0.99, P = .048; and CC vs. GG/GC: adjusted OR = 0.09, 95% CI = 0.01 – 0.72, P = .024), whereas rs2074192 was associated with increased GDM risk (TT vs. CC/CT: adjusted OR = 1.38, 95% CI = 1.08 – 1.75, P = .009). Furthermore, we found that rs6632677 interacted with SBP (P (interaction) = .043) and FPG (P (interaction) = .021) and rs2074192 interacted with HDL-c (P (interaction) = .029) and LDL-c (P (interaction) = .035) to influence the GDM risk of the individual. In the MDR analysis, the rs6632677 was the best one-locus model, and the three-loci model was the best interaction model to predict GDM risk. In addition, functional analysis confirmed that rs2074192 may regulate the splicing process of ACE2 gene. CONCLUSION: ACE2 gene variants are significantly associated with the risk of GDM via gene–gene and gene–environment combinations. The rs2074192 C > T affects the splicing of the ACE2 gene, which may be a potential mechanism leading to the changed susceptibility of an individual female during pregnancy to GDM.
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spelling pubmed-97525652022-12-16 Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population Huang, Gongchen Liang, Qiulian Wang, Yukun Qin, Linyuan Yang, Haili Lin, Lin Yu, Xiangyuan Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: To explore the relationship between angiotensin-converting enzyme 2 (ACE2) genetic variants and gestational diabetes mellitus (GDM) in a southern Chinese population. METHODS: Potential functional variants (rs2106809, rs6632677, and rs2074192) of ACE2 were selected and genotyped in 566 GDM patients and 710 normal pregnaõncies in Guilin, China. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between genetic variant and GDM risk, and then the false positive report probability, multifactor dimensional reduction (MDR), and bioinformatics tools were used to confirm the significant association in the study. RESULTS: After adjusting for age and prepregnancy body mass index, logistic regression analysis showed that ACE2 rs6632677 was significantly associated with a decreased risk of GDM (CC vs. GG: adjusted OR = 0.09, 95% CI: 0.01 – 0.71, P = .023; GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46 – 0.99, P = .048; and CC vs. GG/GC: adjusted OR = 0.09, 95% CI = 0.01 – 0.72, P = .024), whereas rs2074192 was associated with increased GDM risk (TT vs. CC/CT: adjusted OR = 1.38, 95% CI = 1.08 – 1.75, P = .009). Furthermore, we found that rs6632677 interacted with SBP (P (interaction) = .043) and FPG (P (interaction) = .021) and rs2074192 interacted with HDL-c (P (interaction) = .029) and LDL-c (P (interaction) = .035) to influence the GDM risk of the individual. In the MDR analysis, the rs6632677 was the best one-locus model, and the three-loci model was the best interaction model to predict GDM risk. In addition, functional analysis confirmed that rs2074192 may regulate the splicing process of ACE2 gene. CONCLUSION: ACE2 gene variants are significantly associated with the risk of GDM via gene–gene and gene–environment combinations. The rs2074192 C > T affects the splicing of the ACE2 gene, which may be a potential mechanism leading to the changed susceptibility of an individual female during pregnancy to GDM. Frontiers Media S.A. 2022-12-01 /pmc/articles/PMC9752565/ /pubmed/36531495 http://dx.doi.org/10.3389/fendo.2022.1052906 Text en Copyright © 2022 Huang, Liang, Wang, Qin, Yang, Lin and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Huang, Gongchen
Liang, Qiulian
Wang, Yukun
Qin, Linyuan
Yang, Haili
Lin, Lin
Yu, Xiangyuan
Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title_full Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title_fullStr Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title_full_unstemmed Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title_short Association of ACE2 gene functional variants with gestational diabetes mellitus risk in a southern Chinese population
title_sort association of ace2 gene functional variants with gestational diabetes mellitus risk in a southern chinese population
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752565/
https://www.ncbi.nlm.nih.gov/pubmed/36531495
http://dx.doi.org/10.3389/fendo.2022.1052906
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