Table 5.

Neurotransmitter Reuptake and Release Candidate Gene Studies of Methylphenidate Efficacy Published from 2009–2019

Gene	Polymorphism(s)	Authors	Design / Sample	Findings
Dopamine Transporter (DAT/SLC6A3)	3’UTR VNTR	McGough et al 2009 [49]	DBPC N=82 U.S.A	No effect.
	3’UTR VNTR	Froehlich et al 2011 [33]	DBPC N=89 U.S.A.	Diminished MPH response on hyperactive-impulsive symptoms with increasing MPH dose for 10-repeat carriers.
	3’UTR VNTR	Hong et al 2012 [35]	POL N=103 South Korea	No independent effect. Trend toward an interaction with NET −3081 (A/T).
	3’UTR VNTR	Stein et al 2014 [71]	DBPC N=56 U.S.A	Diminished MPH response over time for 9-repeat homozygotes.
	3’UTR VNTR Intron 8 VNTR rs2550948 rs2652511 rs11564750	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	Improved MPH response with rs2550948 G allele. Faster MPH response over time with intron 8 VNTR 6/− or −/− genotypes. No effects for other variants.
	rs460700 rs37020 rs13161905 rs27048 rs6347 rs11133767 rs40184	Pagerols et al 2017 [51]	POL N=107 Spain	No effects.
Norepinephrine Transporter (NET/SLC6A2)	G1287A	McGough et al 2009 [49]	DBPC N=82 U.S.A	No effect.
	G1287A −3081(A/T)	Kim et al 2010 [91]	POL N=112 South Korea	Trend toward improved MPH response for T allele of −3081(A/T). No effect for G1287A.
	G1287A −3081(A/T)	Kim et al 2011 [34] Hong et al 2012 [35]	POL N=102 for Kim et al N=103 for Hong et al South Korea	Kim et al: No effects. Hong et al: No independent effects. NET G1287A*ADRA2A DraI interaction effect (improved response with G allele of G1287A). NET −3081(A/T)*ADRA2A DraI interaction effect (improved response with T allele of −3081(A/T)).
	G1287A −3081(A/T) rs5568 rs998424 rs1616905 rs2242446 rs2242446 and rs1610905 haplotype rs5569 and rs998424 haplotype	Lee et al 2011 [92]	POL N=137 South Korea	No single marker or haplotype effects.
	G1287A	Song et al 2011 [94]	POL N=114 South Korea	Improved MPH response with G1287A G/G homozygosity.
	G1287A −3081(A/T)	Park et al 2012 [95]	POL N=37 South Korea	Improved MPH response with G1287A G/G homozygosity based on clinician but not parent ratings. No effect for −3081(A/T).
	30 tag SNPs G1287A	Thakur et al 2012 [97]	DBPC N=475 Canada	Improved MPH response with rs36021 T allele in children with prenatal smoke exposure. Improved MPH response with rs3785152 C allele in children who lacked prenatal smoke exposure.
	rs192303 rs3785143	Song et al 2014 [76]	POL N=139 South Korea	Improved MPH response with rs192303 C/C homozygosity (not significant after multiple comparison correction). No effect for rs3785143.
	G1287A −3081(A/T)	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effects.
	G1287A −3081(A/T) rs2242446 rs3785143 rs3785157 rs7194256	Angyal et al 2018 [93]	POL N=122 Hungary	Improved MPH response on hyperactive-impulsive symptoms for −3081(A/T) T allele carriers. No independent effects for other variants. Improved MPH response on inattention symptoms for the TCT haplotype of −3081(A/T), rs2242446, and rs3785143 (compared to the ATC haplotype).
Serotonin Transporter (SLC6A4/5-HTT)	5HTTLPR Intron 2 VNTR	McGough et al 2009 [49]	DBPC N=82 U.S.A	Decreased MPH response with Intron 2 VNTR −12/−12 homozygosity. No effect for 5HTTLPR.
	5HTTLPR	Thakur et al 2010 [105]	DBPC N=157 Canada	Improved MPH response with long allele homozygosity.
	5HTTLPR	Park et al 2015 [106]	POL N=114 South Korea	No effect.
	5HTTLPR Intron 2 VNTR	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effects.
Solute Carrier Family 9 (SLC9A9)	rs9810857	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effect.
Synaptosomal-Associated Protein 25 (SNAP25)	T1065G T1069C	McGough et al 2009 [49]	DBPC N=82 U.S.A	No effects.
	T1065G	Song et al 2014 [76]	POL N=139 South Korea	Improved MPH response with T allele (not significant after multiple comparison adjustment).
	T1065G	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	Improved MPH response with G allele (no adjustment for multiple comparisons).

DBPC=double-blind, placebo-controlled

POL=prospective, open-label

SNP=single nucleotide polymorphism

VNTR=Variable nucleotide tandem repeat