PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues

Table 1

Nucleotide variations within coding and regulatory regions of PPARG.

Variant	Disease/trait	Outcome/Association	References
Pro12Ala	T2DM; Insulin resistance	Conflicting results about association to T2DM and insulin resistance. When in LD with C1431T no protection from T2DM development	[57, 73, 83, 85, 87, 89, 102, 104, 105]
	Cardiac disease	Decreased incidence of cardiac disease	[103]
	HDL	Higher HDL cholesterol	[73]
	BMI	Reduction of BMI and fat and lean mass in nonobese (potentiated when in LD with C1431T) and BMI increase in obese individuals	[73, 83, 86, 91, 106]
	LPL	Reduced LPL activity and levels.	[83, 93]
	Leptin	Increased leptin levels	[92, 100]
	Adiponectin	Reduced adiponectin levels	[94, 96, 98, 101]
	Resistin	Reduced resistin levels	[97, 102]
	Bone features	Increase of total bone area and bone mineral content in Ala/Ala mice.	[83]
C1431T	BMI; T2DM; Leptin; Resistin	Increased BMI and fat mass.; Reduced risk of T2DM.; Increased leptin levels.; Increased resistin levels.	[88, 90, 91, 102, 107]
Pro115Gln	BMI	Increased BMI in obese individuals	[108]
[A553ΔAAAiT]	Insulin resistance T2DM Hypertension	In association to 662stop668 mutation in PPP1R3A is responsible of variable hyperinsulinemia, T2DM, hyperlipidemia, hypertension, and dyslipidemia.	[76]
Pro495Leu and Val318Met	Insulin resistance; T2DM; Blood pressure; Partial lipodystrophy; Protein plasma levels	Severe insulin resistance, TD2M, and early-onset hypertension.; Dyslipidemia, preservation of abdominal fat with selective loss of gluteal and limb subcutaneous fat; inability to trap and store NEFA in the postprandial state, hepatic steatosis; reduced adiponectin plasma levels.	[74, 76]
Phe388Leu	Partial lipodystrophy and related features.	Lipodystrophy and dyslipidemia less severe, with absence of fat depots on the upper arms, phlebectasia of limb veins and of hepatic steatosis. Atherosclerosis, polycystic ovarian disease, increased C-peptide concentration, higher insulin resistance.	[77]
Arg425Cys	Partial lipodystrophy T2DM	Diabetes mellitus and hypertriglyceridemia previous to the development of limb and facial lipoatrophy; loss of subcutaneous fat, except for sc truncal fat. Hirsutism in a female carrier.	[109]
Cys114Arg; Cys131Tyr; Cys162Trp; 315Stop; Arg357X	Partial lipodystrophy and related features.	Reduced body fat, partial lipodystrophy of limb and gluteal depots, insulin resistance, hepatic steatosis, severe dyslipidemia, increased triglycerides levels, low HDL levels.; Not for all: early-onset hypertension, cutaneous eruptive Xanthomata, pancreatitis.	[82]
Ser289Cys	Colorectal cancer	Colonic lesions, reduced restraint of cell proliferation both in vitro and in vivo, interference with the inflammatory pathway in tumor tissues and proximal normal mucosa	[84]
A-2819G	T2DM and diabetic retinopathy	Association with T2DM and proliferative retinopathy in diabetic females.	[88]
C-689T; C-681G	BMI; LDL	Increased BMI.; Increased LDL levels.	[95, 99]
A-14G	Partial lipodystrophy; MS	−14G associated with familial partial lipodystrophy subtype 3 (FPLD3). It has been found MS and a relative reduction of gluteal and extremities’fat.	[80]