Association studies of ALOX5 and bone mineral density in healthy adults

Foroud, Tatiana; Ichikawa, Shoji; Koller, Daniel L.; Lai, Dongbing; Curry, Leah R.; Xuei, Xiaoling; Edenberg, Howard J.; Hui, Siu L.; Econs, Michael J.

doi:10.1007/s00198-007-0484-z

Cited by 9 publications

(9 citation statements)

References 31 publications

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“…Spine and total hip BMD values were also entered into a logistic regression model to determine their influence on fracture risk. Computed regression residuals, representing covariate-adjusted study phenotypes, were used in subsequent analyses (30).…”

Section: Discussionmentioning

confidence: 99%

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

Takács

Lazáry

Kósa

et al. 2010

European Journal of Endocrinology

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Objective: Receptor activator of nuclear factor-kB ligand/osteoprotegerin (RANKL/OPG) signaling system plays a crucial role in the regulation of bone resorption. Polymorphic variations in the genes may have an influence on gene expression and bone metabolism. In the present study, we aimed to investigate the influence of RANKL/OPG allelic variations on the in vivo human gene expression of five genes, bone mineral density (BMD), and fracture incidence in Hungarian postmenopausal women. Methods: Three hundred and sixty postmenopausal women (61.6G7.9 years) were genotyped. All together, five single nucleotide polymorphisms (SNPs) in the two genes have been investigated. In addition, bone samples from 17 examined subjects were acquired for gene expression studies. Bone densities and fracture data have also been collected. Results: All two SNPs in OPG gene and three SNPs in RANKL gene showed correlation with BMD. Haplotype analysis of these genes gave similar results. The 'CCT' haplotype of RANKL promoter region, which was associated with decreased BMD, exhibited a significantly upregulated expression of RANKL mRNA, while the other haplotypes of RANKL or OPG 15 genes did not. No correlation between genetic variations and fracture data was found. Conclusion: We have demonstrated associations between RANKL and OPG haplotypes and BMD as well as between RANKL haplotypes and in vivo RANKL expression in a Hungarian postmenopausal population. Moreover, we have found a new RANKL haplotype associating with reduced BMD and increased in vivo RANKL expression in human bone tissue.

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Section: Discussionmentioning

confidence: 99%

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

Takács

Lazáry

Kósa

et al. 2010

European Journal of Endocrinology

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“…Spine, total hip, and radius BMD values were also entered into logistic regression model to determine their influence on fracture risk. Computed regression residuals, representing covariate-adjusted study phenotypes, were used in subsequent analyses (8). Association analyses were performed using the program PedGenie (18), statistical software developed for analyses of pedigrees and independent individuals, computing a statistic equivalent to ANOVA under three genetic models (additive, dominant, and recessive).…”

Section: Data Pre-processing and Statistical Analysismentioning

confidence: 99%

“…More than 200 candidate genes influencing the disease have already been reported (2,3), but the exact genetic background and the interactions among suspected genes as well as genes and environmental or lifestyle factors (4) are still poorly understood (5). Previous studies have also shown that genetic influences can differ among distinct populations and between genders (6)(7)(8). Bone mineral density (BMD) and risk of osteoporotic fracture, predominant study phenotypes in genetic studies, are affected by several genes and their polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in new candidate genes are associated with bone mineral density and fracture risk

Lazáry

Kósa

Tobiás

et al. 2008

European Journal of Endocrinology

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Objective: Osteoporosis (OP) is a multifactorial disease with high heritability but its exact genetic background is still poorly understood. We examined the effect of 24 single nucleotide polymorphisms (SNPs) located in five genes -alkaline phosphatase, matrix metalloproteinase-2, tissue inhibitor of metalloproteases-2 (TIMP2), fibroblast growth factor receptor-1 (FGFR1), and fatty acid-binding protein-3 (FABP3) -previously not associated with OP. Design: We performed a genotype-phenotype association study at a university hospital. Methods: A total of 360 Hungarian postmenopausal women were involved in the study. Bone mineral density (BMD) was determined at spine, hip, and distal radius. Genomic DNA was extracted from venous blood samples and a high-throughput genotyping method based on single-based primer extension was applied for allelic discrimination. Robust statistical tools were utilized for multiplex data analysis. Results: SNP rs6996321 in FGFR1 was significantly related to spine BMD (PZ0.002) and rs10914367 in FABP3 was associated with hip BMD (PZ0.028). Non-vertebral fracture risk was significantly increased in carriers of ' A' allele of rs9900972 in TIMP2 (odds ratioZ2.06, PZ0.0187). We could also identify validated gene-gene interactions significantly affecting BMD and fracture risk. Conclusions: We identified two previously unreported SNPs in FGFR1 and FABP3 associated with BMD and a third SNP in TIMP2 related to risk for non-vertebral osteoporotic fractures. This is the first report about the association between these allelic variants and the phenotypes of postmenopausal OP. Further studies need to clarify the role of these genes and their polymorphisms in the process of bone loss.

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“…Second, previous analyses indicated that there was no evidence of stratification in our sample; therefore, population stratification was unlikely to account for the significant associations found in our population sample. (23) Third, rather than testing only a few SNPs, we tested a range of SNPs that spanned from strong LD to no LD with the most significant The presence and absence of gene expression determined by RT-PCR are denoted by + and −, respectively. Weak, but detectable, amplification is denoted by (+).…”

Section: Discussionmentioning

confidence: 99%

“…(23) The program Haploview (19) was used to examine the extent of LD between the SNPs to ensure that the SNP density was sufficient to evaluate evidence of association. LD (DЈ statistic) was evaluated using one randomly selected individual in each family.…”

Section: Statistical Analysesmentioning

confidence: 99%

Identification of a Linkage Disequilibrium Block in Chromosome 1q Associated With BMD in Premenopausal White Women

Ichikawa

Koller

Curry

et al. 2008

Journal of Bone and Mineral Research

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ABSTRACT:Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD ‫ס‬ 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p ‫ס‬ 1.3 × 10 −6 ) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10 ) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.

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Association studies of ALOX5 and bone mineral density in healthy adults

Abstract: These data do not provide consistent evidence of association between genomic variation in ALOX5 and clinical variability in aBMD in healthy subjects.

Cited by 9 publications

References 31 publications

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

Single nucleotide polymorphisms in new candidate genes are associated with bone mineral density and fracture risk

Identification of a Linkage Disequilibrium Block in Chromosome 1q Associated With BMD in Premenopausal White Women

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