Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Figures & data

Figure 1 Innate immune and host defense mechanisms in the distal airway and alveolus are multi-tiered.

Table 1 Common and Rare Genetic Variants Associated with IPF

Common variants associated with IPF	Gene Function	Gene	Risk Allele(s)	Reference(s)
	Airway mucin production	MUC5B	rs35705950	[^Citation11^–^Citation17,^Citation19^–^Citation21]
		MUC2	rs7934606	[^Citation13,Citation20]
	Cell-cell adhesion	DSP	rs2076295	[^Citation13,Citation20,Citation21,Citation67]
		DPP9	rs12610495	[^Citation13,Citation20,Citation21]
	Toll-like receptor signaling	TOLLIP	rs111521887, rs5743894 rs2743890	[^Citation13,Citation14]
		TLR3	rs3775291 (L412F)	[^Citation97]
		ATP11A	rs1278769	[^Citation13,Citation20,Citation21]
	Cytokine/growth factor signaling	IL1RN	VNTR*2 haplotype block	[^Citation89]
		IL8	rs4073, rs2227307	[^Citation124]
		IL4	rs2243250	[^Citation125,Citation126]
		TGFB1	rs1800470	[^Citation127]
	Telomere maintenance	TERT	rs2736100	[^Citation13,Citation20,Citation21,Citation128]
		OBFC1	rs11191865	[^Citation13]
	Cell cycle regulation	KIF15	rs78238620	[^Citation21]
		MAD1L1	rs12699415	[^Citation21]
		CDKN1A	rs2395655	[^Citation129]
		TP53	rs12951053, rs12602273	[^Citation129]
Rare variants associated with IPF	Gene Function	Gene	Mutation(s)	Reference(s)
	Surfactant production/secretion	SFTPA1	T622C, W211R	[^Citation113,Citation114]
		SFTPA2	G231V, F198S	[^Citation115]
		SFTPC	I73T, M71V, multiple others	[^Citation130,Citation131]
		ABCA3	S1261G, R288K	[^Citation132]
	Telomere maintenance	TERT	L55Q, R901W, T1110M, multiple others	[^Citation133^–^Citation135]
		TERC	98G>A, 37A>G, multiple others	[^Citation133^–^Citation135]
		TINF2	K280E, R282H, R282S	[^Citation136]
		DKC1	T405A, multiple others	[^Citation137]
		RTEL1	R213W, T49M, F964L	[^Citation138,Citation139]
		PARN	A383V, multiple others	[^Citation140]

Figure 2 Genetic variants disrupt TLR/IL-1R family signaling in IPF.

Figure 3 Genetic-driven innate immunity changes contribute to IPF pathogenesis.

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