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The rs2274911 polymorphism in GPRC 6A gene is associated with insulin resistance in normal weight and obese subjects
Author(s) -
Di Nisio Andrea,
Rocca Maria Santa,
Fadini Gian Paolo,
De Toni Luca,
Marcuzzo Giorgio,
Marescotti Maria Cristina,
Sanna Marta,
Plebani Mario,
Vettor Roberto,
Avogaro Angelo,
Foresta Carlo
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13248
Subject(s) - medicine , endocrinology , insulin resistance , insulin , obesity , genotype , biology , gene , genetics
Summary Objective Identification of the novel endocrine role of osteocalcin ( OC ) and its receptor GPRC 6A has given rise to a new branch of research in OC / GPRC 6A axis related to glucose metabolism. GPRC 6A‐ and OC ‐deficient mice share features of the metabolic syndrome, in addition to male infertility. Recently, the polymorphism rs2274911 in GPRC 6A 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). Conclusion In a cohort of normal weight and obese subjects, we found that the nonrare polymorphism rs2274911 in the GPRC 6A gene was associated with insulin resistance features, independently of the metabolic phenotype and OC levels.