Tests of linkage and association of PTH/PTHrP receptor type 1 gene with bone mineral density and height in Caucasians.
Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.S. Caucasian population, we tested linkage or association of the PTHR1 gene with BMD and height. Altogether, 1873 subjects from 405 Caucasian nuclear families were studied. BMD was measured at the lumbar spine (L1-L4) and total hip (femoral neck, trochanter, and intertrochanter regions). Four single nucleotide polymorphisms (SNPs) in the PTHR1 gene were genotyped. Sixteen haplotypes were reconstructed. Only two major haplotypes had frequencies >3% and were thus used for the analysis. Analyses were performed for BMD and height in the total sample and for peak BMD (PBMD) achieved in offspring subjects aged 20-50 in a subsample of 387 nuclear families. We found suggestive evidence for total association between haplotype 13 (AATG) and hip PBMD (P = 0.031). For height, evidence of within-family association was suggested for SNP1, SNP2, and haplotype 4 (GGCA) (P < or = 0.05). Our findings suggest that the PTHR1 gene may be important for PBMD, height variation, or both, although the significance is dampened by correction for multiple testing.
Zhang
Yuan-Yuan
YY
Osteoporosis Research Center, Creighton University Medical Center, 601 N. 30th Street, Suite 6787, Omaha, NE 68131, USA.
Liu
Peng-Yuan
PY
Lu
Yan
Y
Xiao
Peng
P
Liu
Yong-Jun
YJ
Long
Ji-Rong
JR
Shen
Hui
H
Zhao
Lan-Juan
LJ
Elze
Leo
L
Recker
Robert R
RR
Deng
Hong-Wen
HW
D015502:Absorptiometry, Photon; D000328:Adult; D001827:Body Height / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D013131:Spine; D044465:White People / Q000235:genetics
D044168:Receptor, Parathyroid Hormone, Type 1