Table 1.

Summary of genetic studies on troglitazone.

Patients (male/female)	Controls (male/ female)	Country	Ethnicity	Gene (*OMIM)	Gene function	Polymorphism	Comment	Ref.
25(7/18) (abnormal increase in ALT levels)	85 (40/45)	Japan	Asiatic	GSTT1 (*600436)	Catalyze the conjugation and the detoxification of glutathione and reactive toxic compounds, chemicals and metabolites	Wild/null	The combined null genotype of GSTT1 and GSTM1 is a susceptible genetic factor for troglitazone-associated abnormal increases in liver enzyme levels	[75]
				GSTM1 (*138350)		Wild/null
8 patients with Type 2 diabetes with troglitazone- induced liver injury	31 patients unaffected after using troglitazone	Japan	Asiatic	CYP2C19 (*124020)	Enzymatic system responsible for metabolism and elimination of endogenous and exogenous molecules and ingested chemicals	CYP2C19*1 CYP2C19*2 CYP2C19*3	The frequency of CYP2C19 homozygous polymorphism was higher in patients with troglitazone-induced liver injury	[79]
				CYP2D6 (*124030)		CYP2D6*1 CYP2D6*2 CYP2D6*5 CYP2D6*10	The frequency of CYP2D6 polymorphism was identical in both groups
93 women TRIPOD study	–	USA	Hispanic	PPARG (*601487)	Fat cell differentiation and whole-body insulin sensitivity	Pro12Ala	Pro12Ala variant did not account for the prevalence of troglitazone nonresponders in the TRIPOD cohort	[80]
93 women Troglitazone in TRIPOD study	–	USA	Hispanic			rs13073869 rs880663 rs4135263 rs1152003 rs6806708 rs13065455 rs13088205 rs13088214	8 of 131 PPARG variants may underlie response to thiazolidinedione therapy in women at risk for Type 2 diabetes	[81]
3548 subjects enrolled in DPP study	–	USA	Caucasian African- American Hispanic Asian American American Indian			Pro12Ala rs880663, rs4135263 rs1152003 rs6806708 rs13065455	PPARG P12A and the five variants have little or no effect on the beneficial response to troglitazone	[82]
3356 subjects (1116/2240) enrolled in the DPP study	–					Pro12Ala	At 1 year of treatment with troglitazone, Ala12 allele carriers tended to gain more weight than Pro12 allele homozygotes	[84]
3548 subjects enrolled in the DPP study	–			CDKN2A/B (*600160– *600431)	Influence on cell cycle regulatory pathways	rs10811661	Improvement in the functionality of the pancreatic β-cell after 1 year of troglitazone treatment	[85]
3007 subjects (1017/1990) enrolled in DPP study	–			SLC30A8 (*611145)	Zinc transporter and provider in insulin-secreting pancreatic β-cells	rs13266634	No genotype-treatment interactions at 1 year of troglitazone treatment	[86]