Table 1.

Polymorphisms That Influence the Response of ICSs

Gene	Associated Loci	Response Phenotype	Reference
Corticosteroid pathway gene variations
CRHR1	rs242941 rs1876828	Greater increases in lung function in response to corticosteroids	[17,19]
	rs242941	Associated with a negative ΔFEV1% predicted compared to major allele homozygotes and heterozygotes	[20]
NR3C1	ER22/23EK (rs6189 and rs6190)	Significant reduction of transactivating capacity of GRα	[30]
	BclI (rs41423247)	A higher improvement in FEV1 at 4 hours with high-dose ICS	[22]
		Corticosteroid resistance	[32]
	N363S (rs6195)	Associated with an increase in corticosteroid sensitivity	[33]
	TthIIII (rs10052957)	Associated with corticosteroid resistance	[26,35]
STIP1	rs6591838 rs223647 rs6591838 rs1011219	Greater increases in lung function in response to corticosteroids, with the biggest change observed with rs6591838	[41]
FKBP4	rs4713916	Correlated with corticosteroid resistance at least in Crohn’s disease	[43]
DUSP1	rs881152 rs34507926	Associated with greater bronchodilator responses and better asthma control in patients under regular ICS treatment	[49]
HDAC1	rs1741981	Significantly associated with a smaller improvement in FEV1 in response to corticosteroid therapy in asthmatics	[54]
HDAC2	rs58677352	No relationship with possible changes in pulmonary function induced by corticosteroids	[54]
Genetic variation in the pharmacokinetics of corticosteroids
CYP3A	CYP3A4*22 (rs35599367)	Associated with a significant improvement in asthma control scores in patients receiving fluticasone propionate	[57]
	CYP3A5*3 (rs776746)	Related to asthma control scores in subjects under inhaled beclomethasone treatment	[58]
MDR1 (ABCB1)	C1236T (rs1128503) G2677T/A (rs2032582) C3435T (rs1045642)	The initial steroid response in children with nephrotic syndrome may be influenced by genetic variations in MDR1	[16,60]
IPO13		Genetic variation in IPO13 is associated with reduced airway hyperresponsiveness among children with mild-to-moderate asthma who are not using long-term ICSs	[65]
Other genetic variations that can modify the corticosteroid activity
NR1I2	rs3842689	Associated with unresponsiveness to corticosteroids	[66]
TBX21	rs2240017	Improvement in bronchial hyperresponsiveness or better bronchoprotection during ICS treatment	[67]
GLCCI1	rs37972	Significant association with a decreased response to ICS therapy in asthmatic patients	[68]
FBXL7	rs10044254	Associated with improved symptomatic response to ICSs only in children	[72]
ORMDL3	rs2872507 rs72821893	Associated with ICSs treatment response in atopic subjects	[74,75]
VEGFA	rs2146323	Associated with response to ICS therapy in asthma patients	[77]
BBS9	rs2392165	Significant association with ICS use when treating wheezing/coughing, with better ICS response	[80]
FCER2	T2206C (rs28364072)	It can predict low-response to ICS in childhood asthma	[81,82]