ABSTRACT
OBJECTIVE@#To study the relationship between Sonic hedgehog (Shh) associated single-nucleotide polymorphism (SNP) and non-syndromic cleft lip and/or palate (NSCL/P), and to explore the risk factors of cleft lip and/or palate. Many studies suggest that the pathogenesis of NSCL/P could be related to genes that control early development, in which the Shh signaling pathway plays an important role.@*METHODS@#Peripheral blood was collected from 197 individuals (100 patients with NSCL/P and 97 healthy controls). Haploview software was used for haplotype analysis and Tag SNP were selected, based on the population data of Han Chinese in Beijing of the international human genome haplotype mapping project. A total of 27 SNP were selected for the 4 candidate genes of SHH, PTCH1, SMO and GLI2 in the Shh signaling pathway. The genotypes of 27 SNP were detected and analyzed by Sequenom mass spectrometry. The data were analyzed by chi-squared test and an unconditional Logistic regression model.@*RESULTS@#The selected SNP basically covered the potential functional SNP of the target genes, and its minimum allele frequency (MAF) was >0.05: GLI2 73.5%, PTCH1 91.0%, SMO 100.0%, and SHH 75.0%. It was found that the genotype frequency of SNP (rs12674259) located in SMO gene and SNP (rs2066836) located in PTCH1 gene were significantly different between the NSCL/P group and the control group. Linkage disequilibrium was also found on 3 chromosomes (chromosomes 2, 7 and 9) where the 4 candidate genes were located. However, in the analysis of linkage imbalance haplotype, there was no significant difference between the disease group and the control group.@*CONCLUSION@#In China, NSCL/P is the most common congenital disease in orofacial region. However, as it is a multigenic disease and could be affected by multiple factors, such as the external environment, the etiology of NSCL/P has not been clearly defined. This study indicates that Shh signaling pathway is involved in the occurrence of NSCL/P, and some special SNP of key genes in this pathway are related to cleft lip and/or palate, which provides a new direction for the etiology research of NSCL/P and may provide help for the early screening and risk prediction of NSCL/P.
Subject(s)
Humans , Beijing , Case-Control Studies , Cleft Lip , Cleft Palate , Genotype , Hedgehog Proteins , Nucleotides , Polymorphism, Single Nucleotide , Signal TransductionABSTRACT
<p><b>BACKGROUND</b>Pulmonary hypertension (PH) frequently complicates the course of idiopathic pulmonary fibrosis (IPF) patients and is associated with significantly worse outcomes. The aim of the present study was to investigate the incidence of PH in IPF patients and evaluate the correlation between clinical parameters and systolic pulmonary artery pressure (sPAP).</p><p><b>METHODS</b>Hospitalized patients with IPF, who were evaluated for sPAP by Doppler echocardiography from January 2004 to December 2011, were enrolled in our study. Patients were defined as PH by an estimated sPAP > 50 mmHg and graded as PH likely, PH possible and PH unlikely, based on the 2009 European Society of Cardiology/European Respiratory Society PH Guidelines. The correlations between clinical parameters and sPAP were analyzed by multiple linear regression.</p><p><b>RESULTS</b>Totally, 119 IPF patients were enrolled in our study and 28 (23.5%), 20 (16.8%) and 71 (59.7%) patients were PH likely, PH possible and PH unlikely, respectively. Borg dyspnea score was positively correlated with sPAP, r = 0.467, P < 0.001. Oxygen saturation was negatively correlated with sPAP, r = -0.416, P < 0.001. Diffusing capacity of the lung for carbon monoxide percentage predicted was negatively correlated with sPAP, r = -0.424, P = 0.003. N-terminal fragment of pro-brain natriuretic peptide and pulmonary artery width was positively correlated with sPAP, r = 0.452, P = 0.011 and r = 0.513, P < 0.001, respectively.</p><p><b>CONCLUSIONS</b>The incidence of PH in IPF patients was 23.5% in a single center of China. PH may worsen the dyspnea, right heart dysfunction and decrease the life quality of the patients with IPF.</p>