A SYSTEMATIC REVIEW AND META-ANALYSIS OF GENETIC POLYMORPHISMS ASSOCIATED WITH THE RISK OF IDIOPATHIC PULMONARY FIBROSIS

Abstract

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Previously, it was thought that the risk factors that lead to the development of Idiopathic Pulmonary Fibrosis (IPF) were environmental or occupational in nature. However, recent studies have shown that the disease has a strong underlying genetic component. The objective of this review was to identify the genetic polymorphisms associated with the risk of developing IPF. METHODS: The study protocol was registered with PROSPERO (CRD42020181703). We searched PubMed, EBSCO CINAHL Plus, Web of Science, and Wiley Cochrane Library databases for studies on risk factors of IPF published between March 2000 and March 2021. Studies with a diagnosis of IPF based only on the American Thoracic Society and the European Respiratory Society (ATS/ERS) guidelines were included. We assessed the methodological quality of studies using the Newcastle Ottawa Scale (NOS). A meta-analysis for risk of IPF was conducted for MUC5B rs35705950 and IL-4 rs2243250 using the MetaGenyo tool. RESULTS: A total of 23 case-control studies were included with 2945 IPF and 18,500 non-IPF subjects. The quality assessment scores ranged from 6 to 8, suggesting moderate-to-high quality studies and minimal risk of bias. Fourteen studies enrolled biopsy-proven IPF patients, while the remaining nine were diagnosed to have IPF on the basis of clinical and high-resolution computed tomography (HRCT) findings. Seven out of 23 studies were eligible for meta-analysis, MUC5B rs35705950 and IL-4 rs2243250 were the most frequently reported polymorphisms. The allele contrast model (T vs. G) for MUC5B rs35705950 revealed a statistically significant association of T allele with the risk of IPF (OR 4.31, 95% CI 3.27 to 5.68, adjusted P <0.0001), as was the TT + TG vs. GG dominant model (OR 5.60, 95% CI 3.71 to 8.45, adjusted P <0.0001). However, none of the models with IL-4 rs2243250 revealed any association with the risk of IPF. CONCLUSIONS: This review suggests an association of MUC5B rs35705950 T allele with the risk of developing IPF. Genetic screening could play a key role in a population with a family history of IPF. Hence, we recommend further studies in different populations with varying contexts to further explore the role of MUC5B and other genes in the pathogenesis of IPF. CLINICAL IMPLICATIONS: There is a need for more studies with adequate sample size exploring various genes in different context to ascertain the actual association of the genetic polymorphisms that are associated with the risk of IPF. DISCLOSURES: No relevant relationships by Jai Kumar Das, source=Web Response No relevant relationships by Zafar Fatmi, source=Web Response No relevant relationships by Maryam Hassan, source=Web Response No relevant relationships by Salman Kirmani, source=Web Response No relevant relationships by Zahra Ali Padhani, source=Web Response No relevant relationships by Akbar Shoukat, source=Web Response No relevant relationships by Ali Zubairi, source=Web Response