title: The ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism modulates the beneficial effect of weight loss on fasting glucose in non-diabetic individuals.
abstract: OBJECTIVE
  Several studies have reported that the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism (rs1044498) interacts with increased adiposity in affecting glucose homeostasis and insulin sensitivity. Conversely, one would expect that the amelioration of glucose homeostasis observed after weight loss is modulated by the ENPP1 K121Q polymorphism. The aim of our study was to test such hypothesis, in non-diabetic overweight-obese individuals.
  
  
  RESULTS
  Two hundred eleven non-diabetic overweight-obese individuals were studied. Body mass index (BMI), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR index) and lipid levels were obtained before and after 6-week lifestyle intervention (LI; diet and exercise) and their changes calculated as baseline minus 6-week values. LI decreased BMI, glucose, HOMA-IR and triglyceride levels (p < 0.001 for all). No difference across genotype groups (160 KK and 51 KQ or QQ - named as XQ - individuals) was observed in these changes. In a multivariate model, BMI changes predicted fasting glucose changes (β = 0.139 mmol/L (2.50 mg/dl) for 1 unit BMI change, p = 0.005). This correlation was not significant among KK individuals (β = 0.082; p = 0.15), while much steeper and highly significant among XQ individuals (β = 0.336; p = 0.00008) (p-value for Q121-by-weight loss interaction = 0.047).
  
  
  CONCLUSIONS
  Individuals carrying the ENPP1 Q121 variant are highly responsive to the effect of weight loss on fasting glucose. This reinforces the previously suggested hypothesis that the Q121 variant interacts with adiposity in modulating glucose homeostasis.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. marianna.maranghi@uniroma1.it
authors.forename: M
authors.initials: M
authors.lastname: Maranghi
authors.forename: S
authors.initials: S
authors.lastname: Prudente
authors.forename: L
authors.initials: L
authors.lastname: D'Erasmo
authors.forename: E
authors.initials: E
authors.lastname: Morini
authors.forename: E
authors.initials: E
authors.lastname: Ciociola
authors.forename: P
authors.initials: P
authors.lastname: Coletta
authors.forename: A
authors.initials: A
authors.lastname: Verrienti
authors.forename: S
authors.initials: S
authors.lastname: Arciello
authors.forename: M
authors.initials: M
authors.lastname: Copetti
authors.forename: F
authors.initials: F
authors.lastname: Pellegrini
authors.forename: S A
authors.initials: SA
authors.lastname: Santini
authors.forename: S
authors.initials: S
authors.lastname: Morano
authors.forename: S
authors.initials: S
authors.lastname: Filetti
authors.forename: V
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D050154:Adiposity; D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus; D004032:Diet; D015444:Exercise; D005215:Fasting; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000235:genetics; D050177:Overweight / Q000097:blood / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases