OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of the cell division cycle 42 (CDC42) gene with Pulmonary artery systolic pressure (PASP) among patients with Congenital heart disease (CHD). METHODS: In this observational study, clinical data and blood samples were collected from 579 CHD patients with left-to-right shunt who presented to our hospital between January 2012 and January 2017. SNPs of the CDC42 gene were genotyped using an improved multiple ligase detection reaction. Multiple linear regression was applied to evaluate the association of CDC42 gene variants with PASP. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Ethics No.: 20180222-102). RESULTS: Polymorphisms at rs2501256 and rs34896897 of the CDC42 gene were significantly associated with PASP. Compared with the CC genotype at rs2501256, TT and CT carriers displayed higher PASP [TT vs. CC: B (95%CI) = 4.01 (1.95, 6.07), P < 0.001; CT vs. CC: B (95%CI) = 2.91 (0.63, 5.19), P < 0.001]. Similarly, GG and GA genotypes at rs34896897 were associated with higher PASP compared to the AA genotype [GG vs. AA: B (95%CI) = 26.15 (20.45, 31.84), P < 0.001; GA vs. AA: B (95%CI) = 7.19 (4.31, 10.08), P < 0.001]. Genetic model analyses demonstrated significant differences for both rs2501256 and rs34896897 under dominant, additive, and recessive models (P < 0.05). TT carriers at rs2501256 exhibited larger left-and right-atrial diameters, whereas GG carriers at rs34896897 showed greater right-atrial and right-ventricular end-diastolic dimensions. Subgroup analyses revealed no association between rs2501256 and PASP in males, individuals younger than 18 years, Uyghur ethnicity, or those with ventricular septal defects. CONCLUSION CHD patients carrying the minor alleles of rs2501256 and rs34896897 in the CDC42 gene present higher incidence of PASP compared to those carrying the common alleles.
Humans ; Male ; Female ; Heart Defects, Congenital/physiopathology* ; Polymorphism, Single Nucleotide ; cdc42 GTP-Binding Protein/genetics* ; Adult ; Child ; Genotype ; Adolescent ; Child, Preschool ; Genetic Predisposition to Disease ; Pulmonary Artery/physiopathology*

Objective    To explore the prognostic value of serum cystatin C (Cys C) in patients with congenital heart disease-associated pulmonary arterial hypertension (PAH-CHD). Methods    A retrospective cohort study was conducted on adult PAH-CHD patients who were hospitalized for the first time in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to January 2020. The serum Cys C and other related data of patients were collected. The median follow-up time was 57 months. The main end event was all-cause death. According to the prognosis, the patients were divided into a survival group and a death group. Cox regression was used to analyze the risk factors for all-cause death in patients with PAH-CHD. Results    A total of 456 patients were enrolled, including 160 males and 296 females, aged 38.99±14.72 years. The baseline data showed that there were statistical differences in resting heart rate, serum Cys C, creatinine, NT-proB-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C reactive protein (hs-CRP), New York Heart Association (NYHA) cardiac function classification and serum potassium between the survival group and the death group. Univariate Cox regression analysis showed that serum  Cys C, NT-proBNP, hs-cTnT, creatinine and NYHA cardiac function classification were related risk factors for all-cause death in patients with PAH-CHD. Multivariate Cox regression analysis showed that serum Cys C (HR=3.820, 95%CI 2.053-7.108, P<0.001), NYHA grade Ⅲ (HR=2.234, 95%CI 1.316-3.521, P=0.010), NYHA grade Ⅳ (HR=4.037, 95%CI 1.899-7.810, P=0.002) and NT-proBNP (HR=1.026, 95%CI 1.013-1.039, P<0.001) were independent risk factors for all-cause death in patients with PAH-CHD and had a good predictive value. Conclusion    As a new cardiac marker, serum Cys C can predict all-cause death in patients with PAH-CHD and is an independent risk factor.

Objective:To assess the association between maternal smoking, passive exposure to smoking, or paternal smoking in the first trimester and the risk of congenital heart disease (CHD) in offspring.Methods:A meta-analysis was performed on selected case-control studies on parents in the first trimester and CHD involving CHD patients regardless of age or ethnicity, after searching PubMed, Web of Science, Cochrane Library, CNKI, WanFang Data, and China Biology Medicine up to April 2021. The main outcome was CHD confirmed by cardiac ultrasound or cardiac surgery and the quality of included studies was assessed using the Newcastle-Ottawa Scale (≥4 scores). Statistical analysis was carried out using RevMan5.4 software and heterogeneity was determined by Q test combined with I 2 test. In accordance with the heterogeneity test results, the appropriate model (random or fixed) was selected. Subgroup analysis was performed according to the subtype of CHD. Potential publication bias was assessed by funnel plots. Results:A total of 35 studies involving 38 125 subjects were included. The pooled results showed that the risk of CHD in offspring born to mothers who were active or passive smokers in the first trimester was 1.20 ( OR=1.20, 95% CI:1.15-1.26, Z=8.15, P<0.001, I 2=35%) and 1.95 times ( OR=1.95, 95% CI:1.70-2.24, Z=9.52, P<0.001, I 2= 69%) that of non-smoking mothers. The risk of CHD in offspring of fathers who smoked in the first trimester was 1.88 times higher than that of non-smoking parents ( OR=1.88, 95% CI:1.49-2.36, Z=5.39, P<0.001, I 2= 69%). Subgroup analysis indicated an association between active maternal smoking in the first trimester and an increased risk of atrial septal defect ( OR=1.41, 95% CI:1.03-1.92, P=0.030, I 2= 71%) as well as between maternal passive smoking and increased risk of atrioventricular septal defect ( OR=1.76, 95% CI:1.37-2.26, P<0.001, I 2= 11%). Conclusion:Maternal and paternal smoking in the first trimester may both increase the risk of CHD in offspring.