TGFBR2 (rs764522) gene polymorphism cross interaction with gender of cases and controls (n = 175, crude analysis)
TGFBR2 (rs764522) genotype
Female
Male
Cases
Controls
OR (95% CI)
Cases
Controls
OR (95% CI)
C/C
4
18
1.00
10
22
0.49 (0.13–1.82)
C/G
24
37
0.34 (0.10–1.14)
21
23
0.24 (0.07–0.84)
G/G
7
0
0.00
9
0
0.00
P-value
P < 0.0001*
P = 0.0013*
*: P-value significant < 0.05
Declarations
Author contributions
ND: Formal analysis, Investigation, Writing—original draft. ESS and AAHE: Formal analysis, Investigation, Writing—original draft, Writing—review & editing. FRA, IE, and RE: Conceptualization, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
All authors declare that they have no conflicts of interest.
Ethical approval
The Ethical Committee at the Faculty of Medicine, Menoufia University approved the study (No. 11.2/2020 INTM2). The study is in accordance with the ethical standards of institutional research committee and with the 1964 Helsinki Declaration and its later amendments.
Consent to participate
An informed consent was obtained from the parents of all participating subjects of this study.
Consent to publication
Not applicable.
Availability of data and materials
The datasets that support the findings of this study are available from the corresponding author upon reasonable request.
Rahim F, Younas M, Gandapur AJ, Talat A. Pattern of congenital heart diseases in children at tertiary care center in Peshawar.Pakistan J Med Sci. 2003;19:19–22.
Brown KL, Ridout DA, Hoskote A, Verhulst L, Ricci M, Bull C. Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates.Heart. 2006;92:1298–302. [DOI] [PubMed] [PMC]
Peterson C, Dawson A, Grosse SD, Riehle-Colarusso T, Olney RS, Tanner JP, et al. Hospitalizations, costs, and mortality among infants with critical congenital heart disease: How important is timely detection?Birth Defects Res A Clin Mol Teratol. 2013;97:664–72. [DOI] [PubMed] [PMC]
Rashid U, Qureshi AU, Hyder SN, Sadiq M. Pattern of congenital heart disease in a developing country tertiary care center: factors associated with delayed diagnosis.Ann Pediatr Cardiol. 2016;9:210–5. [DOI] [PubMed] [PMC]
Sadiq M, Roshan B, Khan A, Latif F, Bashir I, Sheikh SA. Pattern of pediatric heart diseases in Pakistan.J Coll Physicians Surg Pakistan. 2002;12:149–53.
Diab NS, Barish S, Dong W, Zhao S, Allington G, Yu X, et al. Molecular genetics and complex inheritance of congenital heart disease.Genes (Basel). 2021;12:1020. [DOI] [PubMed] [PMC]
Pierpont ME, Brueckner M, Chung WK, Garg V, Lacro RV, McGuire AL, et al.; American Heart Association Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine. Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association.Circulation. 2018;138:e653–711. [DOI] [PubMed] [PMC]
Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP. Crystal structure of the human TβR2 ectodomain–TGF-β3 complex.Nat Struct Biol. 2002;9:203–8. [DOI] [PubMed]
Takenoshita S, Hagiwara K, Nagashima M, Gemma A, Bennett WP, Harris CC. The genomic structure of the gene encoding the human transforming growth factor β type II receptor (TGF-β RII).Genomics. 1996;36:341–4. [DOI] [PubMed]
Arthur HM, Bamforth SD. TGFβ signaling and congenital heart disease: insights from mouse studies.Birth Defects Res A Clin Mol Teratol. 2011;91:423–34. [DOI] [PubMed]
Robson A, Allinson KR, Anderson RH, Henderson DJ, Arthur HM. The TGFβ type II receptor plays a critical role in the endothelial cells during cardiac development.Dev Dyn. 2010;239:2435–42. [DOI] [PubMed]
Markwald RR, Fitzharris TP, Manasek FJ. Structural development of endocardial cushions.Am J Anat. 1977;148:85–119. [DOI] [PubMed]
Huang F, Li L, Shen C, Wang H, Chen J, Chen W, et al. Association between TGFBR2 gene polymorphisms and congenital heart defects in Han Chinese population.Nutr Hosp. 2015;31:710–5. [DOI] [PubMed]
El-Nabi SH, Sayed S, Abd-Elhafez MA, Elfiky M, Abdel Moneim AE, El-Garawani I. Arg753Gln polymorphisms in the Toll-like receptor 2 gene are associated with cytomegalovirus infection in Egyptian bone marrow recipients.Endocr Metab Immune Disord Drug Targets. 2020;20:619–24. [DOI] [PubMed]
El-Garawani I, Hassab El-Nabi S, Gadallah M, Abdelsameea E. Association between IFN-λ 3 gene polymorphisms and outcome of treatment with direct acting antivirals in chronic HCV-infected Egyptian patients.Immunol Invest. 2021;50:12–22. [DOI] [PubMed]
El-Garawani IM, Shaheen EM, El-Seedi HR, Khalifa SMA, Mersal GAM, Emara MM, et al. Angiotensinogen gene missense polymorphisms (rs699 and rs4762): the association of end-stage renal failure risk with type 2 diabetes and hypertension in Egyptians.Genes (Basel). 2021;12:339. [DOI] [PubMed] [PMC]
Vesnina A, Prosekov A, Kozlova O, Atuchin V. Genes and eating preferences, their roles in personalized nutrition.Genes (Basel). 2020;11:357. [DOI] [PubMed] [PMC]
Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, et al. Heterozygous TGFBR2 mutations in Marfan syndrome.Nat Genet. 2004;36:855–60. [DOI] [PubMed] [PMC]
Tseng ZH, Vittinghoff E, Musone SL, Lin F, Whiteman D, Pawlikowska L, et al. Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease.Heart Rhythm. 2009;6:1745–50. [DOI] [PubMed] [PMC]
Greutmann M, Tobler D. Changing epidemiology and mortality in adult congenital heart disease: looking into the future.Future Cardiol. 2012;8:171–7. [DOI] [PubMed]
Dolk H, Loane M, Garne E; European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005.Circulation. 2011;123:841–9. [DOI] [PubMed]
Hoffman JI. The global burden of congenital heart disease.Cardiovasc J Afr. 2013;24:141–5. [DOI] [PubMed] [PMC]
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2012;380:2095–128. [DOI] [PubMed] [PMC]
Heldin CH, Miyazono K, ten Dijke P. TGF-β signalling from cell membrane to nucleus through SMAD proteins.Nature. 1997;390:465–71. [DOI] [PubMed]
Langlois D, Hneino M, Bouazza L, Parlakian A, Sasaki T, Bricca G, et al. Conditional inactivation of TGF-β type II receptor in smooth muscle cells and epicardium causes lethal aortic and cardiac defects.Transgenic Res. 2010;19:1069–82. [DOI] [PubMed]
Jiao K, Langworthy M, Batts L, Brown CB, Moses HL, Baldwin HS. Tgfβ signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development.Development. 2006;133:4585–93. [DOI] [PubMed]
Hoffman JI, Kaplan S. The incidence of congenital heart disease.J Am Coll Cardiol. 2002;39:1890–900. [DOI] [PubMed]
Li XT, Shen CQ, Zhang R, Shi JK, Li ZH, Liu HY, et al. Association of TGFBR2 rs6785358 polymorphism with increased risk of congenital ventricular septal defect in a Chinese population.Pediatr Cardiol. 2015;36:1476–82. [DOI] [PubMed]
Pugnaloni F, Felici A, Corno AF, Marino B, Versacci P, Putotto C. Gender differences in congenital heart defects: a narrative review.Transl Pediatr. 2023;12:1753–64. [DOI] [PubMed] [PMC]
Buck MB, Knabbe C. TGF-beta signaling in breast cancer.Ann N Y Acad Sci. 2006;1089:119–26. [DOI] [PubMed]
Rossouw JE. Hormones, genetic factors, and gender differences in cardiovascular disease.Cardiovasc Res. 2002;53:550–7. [DOI] [PubMed]