RGD Reference Report - Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women. - Rat Genome Database

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Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women.

Authors: Fairbrother, UL  Tanko, LB  Walley, AJ  Christiansen, C  Froguel, P  Blakemore, AI 
Citation: Fairbrother UL, etal., J Bone Miner Res. 2007 Apr;22(4):544-50.
RGD ID: 10411889
Pubmed: PMID:17243864   (View Abstract at PubMed)
DOI: DOI:10.1359/jbmr.070114   (Journal Full-text)

Leptin is emerging as a key regulator of bone remodeling. In a population-based study of 1306 postmenopausal Danish women, nonsynonymous LEPR SNPs were associated with risk of adiposity, BMD, and vertebral fracture. Smoking exacerbates this LEPR-associated fracture risk. INTRODUCTION: Nonsynonymous single nucleotide polymorphisms (SNPs) in the human LEPR gene have been associated with adiposity in a number of studies, but there have been no large-scale studies of their implications for BMD and osteoporotic fracture risk in postmenopausal women. MATERIALS AND METHODS: We carried out a population-based study of 1430 women. Three well-known nonsynonymous leptin receptor (LEPR) SNPs (Lys109Arg, Gln223Arg, and Lys656Asn) were genotyped for qualitative and quantitative association analysis. Phenotype characteristics of main interest were DXA measures of body fat and lean tissue mass, BMD, and radiographic vertebral fractures. RESULTS: Gln223Arg associated with risk of vertebral fracture (overall OR = 1.76; OR in smokers = 2.31; p = 0.0004), in addition to BMD of the femoral neck and total hip (p = 0.036 and 0.008, respectively). Heterozygote carriers showed lower BMD at both sites. Gln223Arg was also associated with adiposity (p = 0.001 for total fat mass). For adiposity, the at-risk allele was G (resulting in an arginine at position 223). CONCLUSIONS: Variation in LEPR seemed to contribute to the variation in BMD and fracture risk in Danish postmenopausal women; the heterozygous genotype was associated with increased risk of manifest osteoporosis. Further studies are needed to replicate these data and to clarify the mechanisms involved.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Fractures susceptibilityIAGP 10411889DNA:missense mutation:CDS:p.Q223R (human)RGD 
Spinal Fractures susceptibilityISOLEPR (Homo sapiens)10411889; 10411889DNA:SNP:cds:p.Q223R(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)


Additional Information