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Objective:To screen mutations of the adenosine triphosphate(ATP)-binding cassette transporter A3(ABCA3)gene in elderly Chinese individuals with lung interstitial diseases(ILDs)and to analyze the clinical characteristics of ILDs in elderly patients.Methods:A prospective study, After further image analysis of patients diagnosed with interstitial lung diseases between September 2015 and December 2018 at the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, 103 patients were willing to provide peripheral blood samples and signed informed consent.DNA samples were extracted and whole exome sequencing was performed to screen ABCA3 gene mutations.Clinical data of patients were summarized and analyzed.Results:Seven rare variants of the ABCA3 gene were identified in 6 patients, with a mean age of 67 years(69-73 years)and an equal sex distribution, and 33.3%(2/6)were smokers.The most notable presentation was diffuse lung lesions.Patients' final diagnoses included idiopathic pulmonary fibrosis(IPF, 3/6), nonspecific interstitial pneumonia(NSIP, 1/6), and IgG4-related lung disease(2/6). Meanwhile, compound heterozygous mutations of the ABCA3 gene responsible for IPF were identified in patient No.39, including p. Asp1465Asn, p.Leu3Vval and p. Val93Ile3, a new finding in patients with ILDs.Conclusions:ABCA3 mutation-related lung interstitial diseases exhibit variable characteristics, with differences in the age of onset, clinical manifestations, imaging features and prognosis between patients.ABCA3 mutations responsible for early-onset ILDs are mostly homozygous or compound heterozygous and usually highly pathogenic nonsense mutations.In contrast, ABCA3 mutations identified in elderly patients with ILDs are often missense mutations, a possible explanation for the variability of ILDs in the elderly.Since patients with ILDs caused by ABCA3 variants respond poorly to currently available treatment options, early genetic diagnosis may benefit patients by enhancing disease awareness.
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BACKGROUND@#Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1, a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function. The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.@*METHODS@#We performed a case-control study including 296 patients with COPD and 300 healthy individuals. Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis after adjustment for age, gender, and smoking.@*RESULTS@#In total, 28 single-nucleotide polymorphisms were identified in patients with COPD. Among them, "A" allele of rs28491365 (OR: 1.388, 95% CI: 1.055-1.827, P = 0.018), and "G" alleles of rs10512248 (OR: 1.299, 95% CI: 1.021-1.653, P = 0.033) and rs28705285 (OR: 1.359, 95% CI: 1.024-1.803, P = 0.033; respectively) were significantly associated with an increased COPD risk. Genetic model analysis revealed that the "T/T" genotype of rs34695652 was associated with a decreased COPD risk under the recessive model (OR: 0.490, 95% CI: 0.270-0.880, P = 0.010), whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age, gender, and smoking status (OR: 6.364, 95% CI: 1.220-33.292, P = 0.028).@*CONCLUSIONS@#The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.