The Genetics of PTPN1 and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency

Table 1

Summary of human PTPN1 SNP studies and the associated metabolic disorder/parameter investigated. n.s.: not significant.

SNP/polymorphism	Sample size	Associated phenotype	𝑃 value	References
IVS5 + 3666delT, intronic downstream of exon 5	Obese patients 𝑛=711; Nonobese patients 𝑛=427	Morbid obesity (BMI ≥ 40)	𝑃=.02	[11]
rs9144858 C/G, 10 kb downstream of PTPN1	Diabetic patients 𝑛=1227; Normoglycaemic patients 𝑛=1047	Type 2 diabetes	𝑃=.02	[12]
rs9144858 C/G, 10 kb downstream of PTPN1	Moderate obese patients 𝑛=616; Nonobese patients 𝑛=736	Moderate obesity 30 < BMI < 40	𝑃=.04	[12]
IVS6 + G82A, (G82G homozygotes)	From HERITAGE study; White patients 𝑛=502	Increased percent fat; Increased plasma leptin; Increased subcutaneous fat	𝑃=.031; 𝑃=.028; 𝑃=.003	[13]
rs2230604, (Pro303Pro) silent mutation	Chinese children; Obese 𝑛=147; Nonobese 𝑛=118	Increased BMI; Increased waist circumference; Increased serum triglycerides; Higher LDL levels	𝑃=.033; 𝑃=.046; 𝑃=.020; 𝑃=.009	[14]
1484insG, in the 3’ UTR	Italian males 𝑛=335	Increased plasma insulin; Higher HOMA insulin resistance; Increased serum triglycerides	𝑃<.01; 𝑃<.01; 𝑃<.001	[15]
1484insG, in the 3’ UTR	Iranian males 𝑛=412	Increased plasma insulin; Higher total cholesterol; Higher LDL levels; Higher ApoB levels; Higher HOMA insulin resistance	𝑃=.003; 𝑃=.012; 𝑃=.037; 𝑃=.015; 𝑃=.011	[16]
20 unique SNPs within PTPN1, including 1484insG	Hispanic population 𝑛=811	Insulin sensitivity index; Fasting glucose	𝑃=.003- .044; 𝑃≤.001-.029	[17]
P387L, missense mutation	Danish Caucasian population; Type 2 diabetic patients 𝑛=527; Glucose tolerant controls 𝑛=542	Type 2 diabetes	𝑃=.037	[18]
rs6067484, rs6020611, rs1060402	Dutch Caucasian males 𝑛=382	Higher total cholesterol; Higher LDL levels	𝑃<.05; 𝑃<.05	[19]
12 SNPs within PTPN1 coding sequence	American Caucasian population 𝑛=590	Increased coronary calcified plaques	𝑃≤.0001-.043	[20]
g.54281T>A and g.58585T>C, g.−7077G>C	Two Asian populations, Japanese and Chinese 𝑛=1553	Increased BMI; Higher cholesterol	𝑃<.05; 𝑃=.0124	[21]
981C>T	Oji-Cree population 𝑛=728	Lower risk for impaired glucose tolerance or type 2 Diabetes	𝑃=.04	[24]
rs2206656, rs1570179, rs3787345, rs754118, rs3215684, rs2282147, rs718049, and 1484insG	Caucasian type 2 diabetic patients with end-stage renal disease 𝑛=300; Control nondiabetic patients 𝑛=310	Type 2 Diabetes	𝑃=.015-.048	[26]
rs718049	Caucasian female twin population 𝑛=2777	Higher waist circumference; Lower insulin sensitivity; Higher fasting insulin; Higher serum triglycerides; Higher systolic blood pressure	𝑃=.008; 𝑃=.002; 𝑃=.028; 𝑃=.023; 𝑃=.025	[27]
rs1885177	Caucasian female twin population 𝑛=2777	Lower insulin sensitivity	𝑃=.039	[27]
rs6067484, rs1885177, rs2282146, rs718049, rs3787348, and 1484insG	Caucasian female twin population 𝑛=2777	Leptin levels; Body weight; BMI; Total fat	n.s.	[27]
rs6067484, rs6020611, rs3787348, rs1060402	Dutch Caucasian males 𝑛=382	BMI; Total fat; Waist-to-hip ratio	n.s.	[28]
25 SNPs	Pima Indian population; Type 2 diabetic patients 𝑛=573; Nondiabetic patients 𝑛=464	Type 2 diabetes obesity	n.s.	[29]
rs941798, rs3787345, rs2230604 (Pro303Pro), rs2282147, rs718049, rs718050, rs16995309 (Pro387Leu), and rs16989673 (1484insG)	Asian Indian population; Type 2 diabetic patients 𝑛=262; Nondiabetic patients 𝑛=249	Type 2 diabetes	n.s.	[30]
1484insG	Swedish population 𝑛=2309	HOMA insulin resistance; Serum triglyceride levels; BMI; Percent body fat	n.s.	[31]