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Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.

Zhang Y, Liu H, Zhang C, Zhang T, Zhang B, Li L, Chen G, Fu D, Wang K - Sci Rep (2015)

Bottom Line: Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels.Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis.Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

View Article: PubMed Central - PubMed

Affiliation: The First Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

ABSTRACT
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

No MeSH data available.


Related in: MedlinePlus

Association of rs17013181 and rs rs17013182 with serum IBSP level.(a) From left to right, rs17013182, rs17013182 conditioned on genotype A/A of rs17013181, rs17013182 conditioned on genotype A/G of rs17013181, rs17013182 conditioned on genotype G/G of rs17013181. (b) From left to right, rs17013181, rs17013181 conditioned on genotype A/A of rs17013182, rs17013181 conditioned on genotype A/G of rs17013182, rs17013181 conditioned on genotype G/G of rs17013182. The P values of association analyses in combine sample set were indicated for each group.
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f2: Association of rs17013181 and rs rs17013182 with serum IBSP level.(a) From left to right, rs17013182, rs17013182 conditioned on genotype A/A of rs17013181, rs17013182 conditioned on genotype A/G of rs17013181, rs17013182 conditioned on genotype G/G of rs17013181. (b) From left to right, rs17013181, rs17013181 conditioned on genotype A/A of rs17013182, rs17013181 conditioned on genotype A/G of rs17013182, rs17013181 conditioned on genotype G/G of rs17013182. The P values of association analyses in combine sample set were indicated for each group.

Mentions: We determined that several SNPs in the IBSP gene were significantly associated with serum IBSP levels in the combined sample set. However, after conditioning on the two most significant SNPs (rs17013181 and rs17013182), none of the other SNPs showed significance (Table 3). Considering the strong LD between rs17013181 and rs17013182 (r2 = 0.83), we explored the relationship between serum IBSP levels and the combined genotype of the two SNPs (Fig. 2). After conditioning on the effects of rs17013181, we observed that the direction of the effects of rs17013182 was reversed (Table 3 and Fig. 2).


Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.

Zhang Y, Liu H, Zhang C, Zhang T, Zhang B, Li L, Chen G, Fu D, Wang K - Sci Rep (2015)

Association of rs17013181 and rs rs17013182 with serum IBSP level.(a) From left to right, rs17013182, rs17013182 conditioned on genotype A/A of rs17013181, rs17013182 conditioned on genotype A/G of rs17013181, rs17013182 conditioned on genotype G/G of rs17013181. (b) From left to right, rs17013181, rs17013181 conditioned on genotype A/A of rs17013182, rs17013181 conditioned on genotype A/G of rs17013182, rs17013181 conditioned on genotype G/G of rs17013182. The P values of association analyses in combine sample set were indicated for each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645187&req=5

f2: Association of rs17013181 and rs rs17013182 with serum IBSP level.(a) From left to right, rs17013182, rs17013182 conditioned on genotype A/A of rs17013181, rs17013182 conditioned on genotype A/G of rs17013181, rs17013182 conditioned on genotype G/G of rs17013181. (b) From left to right, rs17013181, rs17013181 conditioned on genotype A/A of rs17013182, rs17013181 conditioned on genotype A/G of rs17013182, rs17013181 conditioned on genotype G/G of rs17013182. The P values of association analyses in combine sample set were indicated for each group.
Mentions: We determined that several SNPs in the IBSP gene were significantly associated with serum IBSP levels in the combined sample set. However, after conditioning on the two most significant SNPs (rs17013181 and rs17013182), none of the other SNPs showed significance (Table 3). Considering the strong LD between rs17013181 and rs17013182 (r2 = 0.83), we explored the relationship between serum IBSP levels and the combined genotype of the two SNPs (Fig. 2). After conditioning on the effects of rs17013181, we observed that the direction of the effects of rs17013182 was reversed (Table 3 and Fig. 2).

Bottom Line: Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels.Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis.Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

View Article: PubMed Central - PubMed

Affiliation: The First Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

ABSTRACT
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

No MeSH data available.


Related in: MedlinePlus