Polymorphisms and haplotypes of integrinalpha1 (ITGA1) are associated with bone mineral density and fracture risk in postmenopausal Koreans.
BACKGROUND
ITGA1 is involved in the early remodeling of osteoarthritic cartilage and plays an essential role in the regulation of mesenchymal stem cell proliferation and cartilage production. We investigated the association between bone parameters and ITGA1 polymorphisms and their haplotype linkage disequilibrium (LD) blocks (BL_hts). Genetic susceptibility to osteoporosis was studied in 946 postmenopausal Korean women.


METHODS
We identified 67 genetic polymorphisms in ITGA1 region by direct sequencing (n = 114). Eight SNPs were genotyped to further investigate their potential involvement in osteoporosis in postmenopausal women (n = 946). Areal BMD of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry.


RESULTS
The SNPs, +73187C>T (exon 3) and +76969T>G (intron 5), and their BL_hts were associated with bone mineral density (BMD) at various femur sites (p = 0.009-0.05). Moreover, +159174A>C (intron 28) and its haplotype BL3_ht1 showed a highly significant association with risk of non-vertebral fracture (p = 0.002-0.005) and the minor allele of +159174A>C showed a protective effect.


CONCLUSIONS
These results are suggestive of the association of ITGA1 with osteoporosis and related risk in postmenopausal women.
Lee
Hye-Ja
HJ
Center for Genome Science, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea.
Kim
Shin-Yoon
SY
Koh
Jung-Min
JM
Bok
Jung
J
Kim
Kwang-Joong
KJ
Kim
Kyung-Seon
KS
Park
Mi-Hyun
MH
Shin
Hyoung-Doo
HD
Park
Byung Lae
BL
Kim
Tae-Ho
TH
Hong
Jung Min
JM
Park
Eui Kyun
EK
Kim
Duk Jae
DJ
Oh
Bermseok
B
Kimm
Kuchan
K
Kim
Ghi Su
GS
Lee
Jong-Young
JY
D015519:Bone Density / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D039423:Integrin alpha1