Pharmacogenomics in type II diabetes mellitus management: Steps toward personalized medicine

Figures & data

Table 1 Possible role and effect of variations on metformin therapy

	SLC22A1	SLC22A2	SLC47A1	SLC47A2
Codes	OCT1	OCT2	MATE1	MATE2-K
Site	Hepatocytes, enterocytes	Renal distal tubule	Bile canalicular membrane of hepatocytes and in renal epithelium	Renal epithelium
Action	Mediates metformin uptake, accumulation and pharmacological action in the liver (AMPK activation)	Facilitates urinary elimination of metformin	Metformin secretion in bile and urine	Metformin excretion in urine
Variants	Decreased hepatic and intestinal metformin uptake and accumulation. Decreased AMPK activation. Increased plasma glucose levels and lower insulin levels	Decreased metformin clearance and increased plasma concentration	May affect glucose lowering effects of metformin. With each A allele there is an associated 0.3% HbA1C reduction. G allele has no association with HbA1C reduction

Table 2 Possible role and effects of variations on sulfonylurea treatment goals

	KCNJ11	ABCC8	CYP2C9
Codes	Kir6.2	SUR1	Enzyme in cytochrome P450
Site	KATP channels of pancreas		Liver
Action	SU blocks conductance of KATP channels by interacting with SUR1 and Kir6.2 subunits		Metabolize SU
Variants	Decreased ATP sensitivity and/or pore fixed in the open conformation leading to decreased insulin secretion and subsequent hyperglycemia. Different variations result in different sensitivities to SU	Ser1369Ala variant can influence SU efficacy	Reduced clearance which may correlate to SU toxicity

Abbreviations: ATP, adenosine triphosphate; SU, sulfonylurea.

Table 3 Possible role and effects of variations on TZD therapy

TZD therapy	ACDC	S447S
	Adiponectin	LPL
Action	Protective, plays role in glucose uptake and fatty acid oxidation. Decrease in adiponectin associated with insulin resistance and atherosclerosis	Hydrolyze triglycerides and mediate clearance of atherogenic lipoproteins
Variants	+45GG allele smaller decreases in FPG level, A1C and increase in adiponectin than those with +45T allele Similarly the +276GG genotype when compared to the +276T allele	S447X shows reduced response

Table 4 Possible role and effects of variations on meglitinide therapy

	SLCO1B1	CYP2C9
Action	Possible role in hepatic uptake (transporter)	Metabolization
Variants	521TC, 521CC significantly higher plasma concentrations compared to homozygous TT carriers. Half-life longer in 521CC SNP compared to 521TT	Reduced metabolizing activity in some variations