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Article: Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population

TitleIdentification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2006
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0300-0664
Citation
Clinical Endocrinology, 2006, v. 65 n. 2, p. 198-205 How to Cite?
AbstractObjective: Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified. Methods: We screened for MC4R mutations in 227 obese [body mass index (BMI) 35.29 ± 5.75 kg/m 2] and 100 lean (BMI 21.57 ± 0.29 kg/m 2) southern Chinese subjects using PCR-direct sequencing. In vitro functional studies, including cell surface expression, ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were performed to examine the functional properties of three novel missense mutations. Results: Apart from two previously reported polymorphisms, V103I and -176 A > C, three novel missense heterozygous variants (Y35C, C40R and M218T) were identified. The polymorphisms -176 A > C and Y35C were detected in both obese and normal subjects with similar frequency. C40R was identified only in an obese subject. Pedigree analysis revealed M218T carriers in both lean and obese subjects. The prevalence of V103I carriers in normal-weight controls was significantly higher than that in obese subjects (5.3% vs. 1.3%, P < 0.05). In vitro functional studies showed that all three novel missense variants have normal functions. Conclusions: Two known polymorphisms and three novel variants of the MC4R were identified. No overt functional defects were observed for the three novel MC4R variants, suggesting that they might not be the cause of obesity in variant carriers. © 2006 The Authors.
DescriptionThis paper has been presented in part at the 86th Endocrine Society Annual Meeting held in New Orleans, LA, in 2004
Persistent Identifierhttp://hdl.handle.net/10722/91563
ISSN
2015 Impact Factor: 3.487
2015 SCImago Journal Rankings: 1.314
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRong, Ren_HK
dc.contributor.authorTao, YXen_HK
dc.contributor.authorCheung, BMYen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorCheung, GCNen_HK
dc.contributor.authorLam, KSLen_HK
dc.date.accessioned2010-09-17T10:21:25Z-
dc.date.available2010-09-17T10:21:25Z-
dc.date.issued2006en_HK
dc.identifier.citationClinical Endocrinology, 2006, v. 65 n. 2, p. 198-205en_HK
dc.identifier.issn0300-0664en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91563-
dc.descriptionThis paper has been presented in part at the 86th Endocrine Society Annual Meeting held in New Orleans, LA, in 2004-
dc.description.abstractObjective: Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified. Methods: We screened for MC4R mutations in 227 obese [body mass index (BMI) 35.29 ± 5.75 kg/m 2] and 100 lean (BMI 21.57 ± 0.29 kg/m 2) southern Chinese subjects using PCR-direct sequencing. In vitro functional studies, including cell surface expression, ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were performed to examine the functional properties of three novel missense mutations. Results: Apart from two previously reported polymorphisms, V103I and -176 A > C, three novel missense heterozygous variants (Y35C, C40R and M218T) were identified. The polymorphisms -176 A > C and Y35C were detected in both obese and normal subjects with similar frequency. C40R was identified only in an obese subject. Pedigree analysis revealed M218T carriers in both lean and obese subjects. The prevalence of V103I carriers in normal-weight controls was significantly higher than that in obese subjects (5.3% vs. 1.3%, P < 0.05). In vitro functional studies showed that all three novel missense variants have normal functions. Conclusions: Two known polymorphisms and three novel variants of the MC4R were identified. No overt functional defects were observed for the three novel MC4R variants, suggesting that they might not be the cause of obesity in variant carriers. © 2006 The Authors.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0300-0664en_HK
dc.relation.ispartofClinical Endocrinologyen_HK
dc.rightsClinical Endocrinology. Copyright © Blackwell Publishing Ltd.-
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAdulten_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshChinaen_HK
dc.subject.meshCyclic AMP - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHeterozygoteen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMutagenesis, Site-Directeden_HK
dc.subject.meshMutation, Missenseen_HK
dc.subject.meshObesity - genetics - metabolismen_HK
dc.subject.meshPedigreeen_HK
dc.subject.meshPolymorphism, Geneticen_HK
dc.subject.meshPolymorphism, Restriction Fragment Lengthen_HK
dc.subject.meshReceptor, Melanocortin, Type 4 - genetics - metabolismen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshTransfection - methodsen_HK
dc.titleIdentification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese populationen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, BMY:mycheung@hku.hken_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL:ksllam@hku.hken_HK
dc.identifier.authorityCheung, BMY=rp01321en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1365-2265.2006.02573.xen_HK
dc.identifier.pmid16886960-
dc.identifier.scopuseid_2-s2.0-33746040561en_HK
dc.identifier.hkuros129066-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33746040561&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue2en_HK
dc.identifier.spage198en_HK
dc.identifier.epage205en_HK
dc.identifier.eissn1365-2265-
dc.identifier.isiWOS:000239107800010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridRong, R=7003938735en_HK
dc.identifier.scopusauthoridTao, YX=7402420424en_HK
dc.identifier.scopusauthoridCheung, BMY=7103294806en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridCheung, GCN=49762948800en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.citeulike765648-

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