CONTEXT: Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations. OBJECTIVE: Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL. SUBJECTS AND METHODS: Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively. RESULTS: Single-marker and haplotype analyses revealed that ESR2 and latent TGF-beta binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P=0.0004) and prevalent fracture (P=0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture. CONCLUSIONS: Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture.
CONTEXT: Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations. OBJECTIVE: Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL. SUBJECTS AND METHODS: Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively. RESULTS: Single-marker and haplotype analyses revealed that ESR2 and latent TGF-beta binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P=0.0004) and prevalent fracture (P=0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture. CONCLUSIONS: Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture.
Authors: Aditi Mukherjee; Emily A Larson; Amy S Carlos; John K Belknap; Peter Rotwein; Robert F Klein Journal: J Bone Miner Res Date: 2012-06 Impact factor: 6.741
Authors: Manir Ali; Martin McKibbin; Adam Booth; David A Parry; Payal Jain; S Amer Riazuddin; J Fielding Hejtmancik; Shaheen N Khan; Sabika Firasat; Mike Shires; David F Gilmour; Katherine Towns; Anna-Louise Murphy; Dimitar Azmanov; Ivailo Tournev; Sylvia Cherninkova; Hussain Jafri; Yasmin Raashid; Carmel Toomes; Jamie Craig; David A Mackey; Luba Kalaydjieva; Sheikh Riazuddin; Chris F Inglehearn Journal: Am J Hum Genet Date: 2009-04-09 Impact factor: 11.025