Understanding Idiopathic Interstitial Pneumonia: A Gene-Based Review of Stressed Lungs

Table 2

Genes with polymorphisms predisposing to IIP in multiple studies, expressing pulmonary cells, function, and mutational consequences.

Gene	Expressing cells in lung	Gene function	Risk allele	Effect of risk allele	Cellular consequence
IL1RN	Bronchus epithelium [160]; Alveolar epithelium [161]; Immune cells [162]	Inhibitor of proinflammatory effect of IL-1α and IL-1β [163]	VNTR2 haploblock [78]^#	Decreased expression [78]	Increase of IL-1β/Il-1Ra ratio with proinflammatory/fibrotic effect [74]
TERT	AEC type II [123]; Lung fibroblasts [124]; Lung epithelial cells [126]	Enzyme in telomerase complex maintaining telomere length [127–130]	rs2736100 major A allele [86, 97, 98, 164]	?	?
MUC5B	Airway submucosal glands [165]; Macrophages [166]	Influence on rheological properties of airway mucus, mucociliary transport, and airway defense [93, 165]	rs35705950 minor T allele [83, 84, 86, 87, 96, 98, 100, 164, 167–169]	Expression ↑ [83]	Lower bacterial burden [93, 94]; Improved macrophage function [93]
LRRC34	Not detected in human lung [170]	?	rs6793295 minor C allele [86, 98]	?	?
FAM13A	Lung tissue [99]	?	rs2609255 minor G allele [86, 98]	?; No upregulation in lung tissue [98]	?
IVD	?	Mitochondrial matrix enzyme involved in leucine catabolism [98]	rs2034650 major T allele [86, 98]	?; No upregulation in lung tissue [98]	?

Pooled meta-analysis of five independent cohorts [74–77].