A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology

Table 1

Summary of genes and their SNPs which might have possible clinical effects towards MTX.

	Gene		SNP(s)	Possible clinical effects
Transporting proteins	RFC1 [31–34]		G80A	Increasing/decreasing intracellular MTX level
	ABC family	ABCB1 [28, 29, 38]	C3435T	Affecting efficacy of MTX
			C1236T	Affecting the distribution of MTX and incidence of hematological toxicity
		ABCC1 [47, 48]	rs246240S	Association with MTX related toxicity
			rs3784862
		ABCC2 [29, 45]	A2412G	Leading to accumulation of MTX to nephrotoxic levels
			G1249A	Association with MTX related gastrointestinal toxicity
			G1058A	Association with MTX related hepatotoxicity
		ABCC4 [28]	C934A	Association with MTX related hematological toxicity
Metabolizing enzymes	MTHFR [39–44]		C677T	Affecting the toxicity but not the efficacy by resulting in a lower enzyme activity; association with related nephrotoxicity, anemia, and neurologic side effects
			A1298C
	ATIC [49–51]		C347G	Affecting efficacy and toxicity of MTX
	TYMS [52, 53]		5′-UTR 28-bp repeat	Affecting efficacy and toxicity of MTX
			3′-UTR 6-bp deletion	Affecting efficacy of MTX.
	GGH [46, 54, 55]		C452T	Affecting efficacy of MTX
			C401T
	DHFR [29, 45]		T721A	Affecting efficacy of MTX
			C830T
	MS [29, 45, 54]		A2756G	Association with MTX associated toxicity
	MTRR [29, 45, 51]		A66G	Association with MTX associated toxicity