Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese.
BACKGROUND
Chromosome 1p36 is a region that has previously shown good evidence of linkage to bone mineral density (BMD) in multiple studies, but the genes that are responsible for the linkage signals are unknown.


METHODS
We performed a gene-wide and tag SNP-based association study of four positional and functional candidate genes (TNFRSF1B, PLOD, CNR2, and MTHFR) at 1p36 in 1, 243 case-control Chinese subjects. Twenty-three tag SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Binary logistic regression analyses were performed to test for genotype associations between each SNP and BMD. Allelic and haplotype association analyses were conducted by Haploview. Gene-gene interactions were investigated using multifactor dimensionality reduction method.


RESULTS
The PLOD rs7529452 (C385T; F98F) and MTHFR rs1801133 (C677T; A429E) showed significant genotypic/allelic associations with BMDs at all sites measured (P=0.08-0.001), and a promising two-locus gene-gene interaction for femoral neck BMD. The CNR2 rs2501431 (A592G; G155G) showed nominally significant allelic associations with trochanter and hip BMD. The TNFRSF1B rs976881 showed genotypic associations with BMDs (P=0.08-0.04).


CONCLUSIONS
Our results suggest that multiple genes at 1p36, individually or in different combinations, contribute to osteoporosis susceptibility in Chinese.
Huang
Qing-Yang
QY
Department of Medicine, The University of Hong Kong, Hong Kong. huangqy@hkucc.hku.hk
Li
Gloria H Y
GH
Kung
Annie W C
AW
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics; D043882:Receptors, Cannabinoid / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics
D043882:Receptors, Cannabinoid; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)