Association of protein tyrosine phosphatase 1B gene polymorphism with the effects of weight reduction therapy on bodyweight and glycolipid profiles in obese patients

J Diabetes Investig. 2021 Aug;12(8):1462-1470. doi: 10.1111/jdi.13492. Epub 2021 Feb 5.

Abstract

Aims/introduction: Weight reduction therapy is the primary treatment to prevent complications of obesity, such as lifestyle diseases and cardiovascular disease; however, to date, useful methods and genetic factors for predicting the outcomes of weight reduction therapy in obese patients have not been established. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator for insulin and leptin signaling, potentially modulates glucose and energy homeostasis. This study aimed to investigate the contribution of PTPN1 polymorphisms on weight reduction and diabetes in obese Japanese patients.

Materials and methods: PTPN1-tagged single-nucleotide polymorphisms (SNPs) rs3787348 and rs6067484 were genotyped in 447 obese Japanese patients from the general population. In this prospective cohort study, all obese patients underwent a 3-month weight reduction therapy with lifestyle modifications, as recommended by guidelines.

Results: In obese patients (male/female 196/251, age 50 ± 15 years, body mass index [BMI] 32 ± 6 kg/m2 ), the minor allele appeared at a frequency of 45.5% in rs3787348 SNP of the PTPN1 gene. The T allele of rs3787348 was significantly associated with a higher BMI (P = 0.041 in the additive model). The patients with the T allele in SNP rs3787348 of PTPN1 had significantly smaller reductions in BMI, bodyweight and waist circumference levels during weight reduction therapy (BMI G/G, -1.9 ± 0.2; G/T, -1.5 ± 0.1; T/T, -1.2 ± 0.1; P = 0.001 in the additive model).

Conclusions: Our findings show that the SNP rs3787348 in PTPN1 was associated with the effects of weight reduction therapy on BMI and waist circumference among obese Japanese patients.

Keywords: Obesity; Protein tyrosine phosphatase 1B; Weight reduction therapy.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Body Mass Index
  • Body Weight / genetics*
  • Cohort Studies
  • Energy Metabolism
  • Female
  • Glycolipids / blood*
  • Humans
  • Japan
  • Life Style
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Obesity / therapy*
  • Polymorphism, Genetic / genetics
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics*
  • Waist Circumference
  • Weight Loss / genetics*

Substances

  • Glycolipids
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1