Content area
Full Text
About the Authors:
Hélène Choquet
* E-mail: [email protected]
Affiliations Ernest Gallo Clinic and Research Center, Emeryville, California, United States of America, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America, Department of Anesthesia, University of California San Francisco, San Francisco, California, United States of America
Jay Kasberger
Affiliation: Ernest Gallo Clinic and Research Center, Emeryville, California, United States of America
Ajna Hamidovic
Affiliation: Department of Preventive Medicine, Northwestern University, Chicago, Illinois, United States of America
Eric Jorgenson
Affiliations Ernest Gallo Clinic and Research Center, Emeryville, California, United States of America, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
Introduction
Obesity is a common disorder which affects more than 35% of American adults [1] and involves multiple genetic factors [2], [3]. The PCSK1 (Prohormone Convertase Subtilisin/Kexin type 1) gene is involved in regulation of appetite and consequently in obesity via the biochemical activities of its protein (PC1/3) on key peptides in the leptin-melanocortin pathway [4].
Rare PCSK1 variants causing total or partial PC1/3 deficiency have been reported to be associated with extreme obesity [5], [6], [7], [8], [9]. Furthermore, common PCSK1 variants (notably rs6232 and rs6234-rs6235) have been shown to contribute to obesity risk in a study of 13,659 European subjects [10]. Thus, PCSK1 is considered to play a role in this common disorder. To date, several replication studies have been undertaken in European [11], [12], [13], [14], Asian [15], [16], [17] and Mexican [18] populations. Nevertheless, there is mixed evidence for the association of the rs6232, rs6234 and rs6235 PCSK1 variants with overweight, obesity and body mass index (BMI).
In Europeans, a first study found a modest association of rs6232 with BMI and obesity in young subjects (age <59 years) from Norfolk, UK [12]. A second study found no significant association between rs6235 and obesity in 3,885 Swedish non-diabetic subjects [11]. A third study reported the association of rs6232 with an increased risk of overweight, and the association of rs6235 with an increased risk of obesity in 3,925 Danish subjects [13]. The initial association of rs6234 with obesity has been recently replicated in 979 Greek subjects [14]. Finally, the GIANT consortium (Genetic Investigation of ANthropometric Traits) detected a modest association between rs6232...