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Article: Genetic variants in GREM2 are associated with bone mineral density in a southern Chinese population

TitleGenetic variants in GREM2 are associated with bone mineral density in a southern Chinese population
Authors
Issue Date2013
PublisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.org
Citation
Journal of Clinical Endocrinology and Metabolism, 2013, v. 98 n. 9, p. E1557-E1561 How to Cite?
AbstractCONTEXT: Gremlin 2 (GREM2) is a regulator of osteoblast differentiation and osteogenesis. A recent genome-wide association study identified GREM2 as a novel susceptibility gene for trabecular volumetric bone mineral density (BMD). OBJECTIVE: We investigated whether GREM2 gene variants were associated with areal BMD in southern Chinese people. RESEARCH DESIGN AND METHODS: We genotyped 108 single-nucleotide polymorphisms (SNPs) in 417 cases (defined as BMD Z-score ≤-1.28) and 359 controls (defined as BMD Z-score ≥+1). Multivariable logistic regression using an additive model was used to evaluate the association. The most associated SNPs of BMD at the spine, femoral neck, and total hip was then replicated in an additional 454 cases and 401 controls. RESULTS: Twelve, 13, and 14 SNPs showed nominal association with BMD at the spine, femoral neck, and total hip, respectively. The minor alleles of rs9728351 (odds ratio [OR] = 2.56; 95% confidence interval [CI] = 1.33-4.92), rs11588607 (OR = 1.65; 95% CI = 1.14-2.4), and rs4454537 (OR = 1.87; 95% CI = 1.22-2.86) were associated with the low BMD at the spine, femoral neck, and total hip, respectively. Among these SNPs most associated with BMD, rs4454537 was successfully replicated in an independent cohort (OR = 1.59; 95% CI = 1.05-2.4). Meta-analysis showed that the minor allele of rs4454537 was associated with low total hip BMD with an OR of 1.72 (95% CI = 1.28-2.31) (P = 3.2 × 10(-4); P(corrected) = .043). CONCLUSIONS: The minor allele of rs4454537 is significantly associated with low BMD at the total hip of southern Chinese people. Our study further suggests GREM2 as a novel susceptibility gene for osteoporosis
Persistent Identifierhttp://hdl.handle.net/10722/193881
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.940
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, CLen_US
dc.contributor.authorLau, KSen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorTan, KCBen_US
dc.contributor.authorKung, AWCen_US
dc.date.accessioned2014-01-28T06:30:45Z-
dc.date.available2014-01-28T06:30:45Z-
dc.date.issued2013en_US
dc.identifier.citationJournal of Clinical Endocrinology and Metabolism, 2013, v. 98 n. 9, p. E1557-E1561en_US
dc.identifier.issn0021-972X-
dc.identifier.urihttp://hdl.handle.net/10722/193881-
dc.description.abstractCONTEXT: Gremlin 2 (GREM2) is a regulator of osteoblast differentiation and osteogenesis. A recent genome-wide association study identified GREM2 as a novel susceptibility gene for trabecular volumetric bone mineral density (BMD). OBJECTIVE: We investigated whether GREM2 gene variants were associated with areal BMD in southern Chinese people. RESEARCH DESIGN AND METHODS: We genotyped 108 single-nucleotide polymorphisms (SNPs) in 417 cases (defined as BMD Z-score ≤-1.28) and 359 controls (defined as BMD Z-score ≥+1). Multivariable logistic regression using an additive model was used to evaluate the association. The most associated SNPs of BMD at the spine, femoral neck, and total hip was then replicated in an additional 454 cases and 401 controls. RESULTS: Twelve, 13, and 14 SNPs showed nominal association with BMD at the spine, femoral neck, and total hip, respectively. The minor alleles of rs9728351 (odds ratio [OR] = 2.56; 95% confidence interval [CI] = 1.33-4.92), rs11588607 (OR = 1.65; 95% CI = 1.14-2.4), and rs4454537 (OR = 1.87; 95% CI = 1.22-2.86) were associated with the low BMD at the spine, femoral neck, and total hip, respectively. Among these SNPs most associated with BMD, rs4454537 was successfully replicated in an independent cohort (OR = 1.59; 95% CI = 1.05-2.4). Meta-analysis showed that the minor allele of rs4454537 was associated with low total hip BMD with an OR of 1.72 (95% CI = 1.28-2.31) (P = 3.2 × 10(-4); P(corrected) = .043). CONCLUSIONS: The minor allele of rs4454537 is significantly associated with low BMD at the total hip of southern Chinese people. Our study further suggests GREM2 as a novel susceptibility gene for osteoporosisen_US
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.org-
dc.relation.ispartofJournal of Clinical Endocrinology and Metabolismen_US
dc.titleGenetic variants in GREM2 are associated with bone mineral density in a southern Chinese populationen_US
dc.typeArticleen_US
dc.identifier.emailCheung, CL: lung1212@hku.hken_US
dc.identifier.emailLau, KS: kslau@hku.hken_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.emailTan, KCB: kcbtan@hku.hken_US
dc.identifier.emailKung, AWC: awckung@hku.hken_US
dc.identifier.authorityCheung, CL=rp01749en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityTan, KCB=rp00402en_US
dc.identifier.authorityKung, AWC=rp00368en_US
dc.identifier.doi10.1210/jc.2013-1983en_US
dc.identifier.pmid23902946-
dc.identifier.hkuros227571en_US
dc.identifier.volume98en_US
dc.identifier.issue9-
dc.identifier.spageE1557en_US
dc.identifier.epageE1561en_US
dc.identifier.isiWOS:000324175200016-
dc.publisher.placeUnited States-

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