title: The rs2274911 polymorphism in GPRC6A gene is associated with insulin resistance in normal weight and obese subjects.
abstract: OBJECTIVE
  Identification of the novel endocrine role of osteocalcin (OC) and its receptor GPRC6A has given rise to a new branch of research in OC/GPRC6A axis related to glucose metabolism. GPRC6A- and OC-deficient mice share features of the metabolic syndrome, in addition to male infertility. Recently, the polymorphism rs2274911 in GPRC6A was shown to be associated with testicular impairment. We aimed to investigate the role of rs2274911 polymorphism in glucose and lipid metabolism in a cohort of normal weight and obese subjects DESIGN, PATIENTS, SETTINGS: A total of 392 male and females, including 218 obese patients and 174 age-matched normal weight controls, were retrospectively selected.
  
  
  RESULTS
  The distribution of rs2274911 alleles and genotypes did not differ either between normal weight and obese subjects or sexes (all P > 0·05). Age- and OC-adjusted multivariate analysis revealed that, in the normal weight group, fasting insulin and HOMA-IR increased in GA (P = 0·016 and P = 0·025) and AA genotypes (P = 0·033 and P = 0·040) compared with GG homozygotes. In the obese group, AA homozygotes had increased fasting glucose (P = 0·041 vs GG). Triglycerides, fasting insulin and HOMA-IR increased in both GA (P = 0·020, P < 0·001 and P = 0·001) and AA genotype (P = 0·021, P = 0·013 and P = 0·013).
  
  
  CONCLUSIONS
  In a cohort of normal weight and obese subjects, we found that the nonrare polymorphism rs2274911 in the GPRC6A gene was associated with insulin resistance features, independently of the metabolic phenotype and OC levels.
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Nisio
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: Maria Santa
authors.initials: MS
authors.lastname: Rocca
authors.affiliation: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, Service of Preventive Medicine, University of Padova, Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marcuzzo
authors.affiliation: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marescotti
authors.affiliation: Department of Medicine, Internal Medicine, University of Padova, Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanna
authors.affiliation: Department of Medicine, Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Department of Medicine, Internal Medicine, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.affiliation: Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000328:Adult; D000483:Alleles; D001835:Body Weight / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C488584:GPRC6A protein, human; D043562:Receptors, G-Protein-Coupled