Polymorphisms of VEGF, TGFβ1, TGFβR2 and conotruncal heart defects in a Chinese population.
Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI 0.24-0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Enshi
E
Wang
Zhenhua
Z
Wang
Shenghua
S
Liu
Haiyong
H
Gu
Dingxu
D
Gong
Kun
K
Hua
Yu
Y
Nie
Jue
J
Wang
Haoran
H
Wang
Jie
J
Gong
YuJian
Y
Zhang
Hui
H
Zhang
Ruiping
R
Liu
Shengshou
S
Hu
Hao
H
Zhang
D044466:Asian People; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D013771:Tetralogy of Fallot / Q000235:genetics / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014188:Transposition of Great Vessels / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II