Bone structural effects of variation in the TNFRSF1B gene encoding the tumor necrosis factor receptor 2.
The 1p36 region of the human genome has been identified as containing a QTL for BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which encodes the TNF receptor 2, in two large population-based cohorts. Our results suggest that variation in TNFRSF1B is associated with BMD.


BACKGROUND
The TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional candidate gene for impaired bone structure through the role that TNF has in bone cells. The aims of this study were to evaluate the role of variations in the TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal women.


METHODS
Six SNPs in TNFRSF1B were analysed in a cohort of 1,190 postmenopausal Australian women, three of which were also genotyped in an independent cohort of 811 UK postmenopausal women. Differences in phenotypic means for genotype groups were examined using one-way ANOVA and ANCOVA.


RESULTS
Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in the UK population (P = 0.005 - 0.029). Significant associations were also observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002 - 0.003). We then combined the data from the two cohorts and observed significant associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P = 0.002 - 0.033).


CONCLUSIONS
Genetic variation in TNFRSF1B plays a role in the determination of bone structure in Caucasian postmenopausal women, possibly through effects on osteoblast and osteoclast differentiation.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009.
B H
BH
Mullin
R L
RL
Prince
I M
IM
Dick
F M A
FM
Islam
D J
DJ
Hart
T D
TD
Spector
A
A
Devine
F
F
Dudbridge
S G
SG
Wilson
D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood; D001315:Australia / Q000453:epidemiology; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000235:genetics* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
D000596:Amino Acids; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D015675:Osteocalcin; C036020:deoxypyridinoline