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Significant association of SREBP-2 genetic polymorphisms with avascular necrosis in the Korean population.

Kim TH, Baek JI, Hong JM, Choi SJ, Lee HJ, Cho HJ, Park EK, Kim UK, Kim SY - BMC Med. Genet. (2008)

Bottom Line: SREBP-2 plays a central role in the maintenance of lipid homeostasis through stimulating expression of genes associated with cholesterol biosynthetic pathways.In contrast, rs1052717 and rs2267443 polymorphisms were significantly associated with AVN risk.This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2 Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea. archion@knu.ac.kr

ABSTRACT

Background: It is known that steroid usage and alcohol abuse are major etiological factors in the development of avascular necrosis (AVN), a bone disease that produces osteonecrosis of the femoral head. The facilitation of fat biosynthesis by steroids and alcohol disrupts the blood supply into the femoral head. SREBP-2 plays a central role in the maintenance of lipid homeostasis through stimulating expression of genes associated with cholesterol biosynthetic pathways. The aim of this study was to examine the association between the polymorphisms of the SREBP-2 gene and AVN susceptibility in the Korean population.

Methods: Four single nucleotide polymorphisms (SNP) in the SREBP-2 gene, IVS1+8408 T>C (rs2267439), IVS3-342 G>T (rs2269657), IVS11+414 G>A (rs1052717) and IVS12-1667 G>A (rs2267443), were selected from public databases and genotyped in 443 AVN patients and 273 control subjects by using single-based extension (SBE) genotyping.

Results: The minor allele (C) frequency of rs2267439 showed a significant protective effect on AVN (P = 0.01, OR; 0.75, 95% CI; 0.604-0.935), and the genotype frequencies of this polymorphism were also different from the controls in all alternative analysis models (P range, 0.009-0.03, OR; 0.647-0.744). In contrast, rs1052717 and rs2267443 polymorphisms were significantly associated with AVN risk. Further analysis based on pathological etiology showed that the genotypes of rs2267439, rs1052717 and rs2267443 were also significantly associated with AVN susceptibility in each subgroup.

Conclusion: This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.

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Linkage disequilibrium coefficients and haplotypes of SREBP-2 polymorphisms A. Linkage disequilibrium (LD) among SREBP-2 polymorphisms.B. LD coefficients (/ D'/ and r2) between SREBP-2 polymorphisms. C. Haplotypes and their frequencies between two linked SNPs, rs2269657 and rs1052717, in a LD block.
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Figure 1: Linkage disequilibrium coefficients and haplotypes of SREBP-2 polymorphisms A. Linkage disequilibrium (LD) among SREBP-2 polymorphisms.B. LD coefficients (/ D'/ and r2) between SREBP-2 polymorphisms. C. Haplotypes and their frequencies between two linked SNPs, rs2269657 and rs1052717, in a LD block.

Mentions: To investigate the association of SREBP-2 gene polymorphisms with AVN, we selected four intronic SNPs, rs2267439, rs2269657, rs1052717 and rs2267443, from public databases by considering their allele frequencies and positions, and analyzed these polymorphisms in 443 AVN patients and 273 control subjects. LD coefficients (/D'/) and r2 were calculated, and rs2269657 and rs1052717 demonstrated tight LD (Fig. 1A and 1B). The haplotypes and their frequencies in the LD block between rs2269657 and rs1052717 are showed in Figure 1C.


Significant association of SREBP-2 genetic polymorphisms with avascular necrosis in the Korean population.

Kim TH, Baek JI, Hong JM, Choi SJ, Lee HJ, Cho HJ, Park EK, Kim UK, Kim SY - BMC Med. Genet. (2008)

Linkage disequilibrium coefficients and haplotypes of SREBP-2 polymorphisms A. Linkage disequilibrium (LD) among SREBP-2 polymorphisms.B. LD coefficients (/ D'/ and r2) between SREBP-2 polymorphisms. C. Haplotypes and their frequencies between two linked SNPs, rs2269657 and rs1052717, in a LD block.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2600781&req=5

Figure 1: Linkage disequilibrium coefficients and haplotypes of SREBP-2 polymorphisms A. Linkage disequilibrium (LD) among SREBP-2 polymorphisms.B. LD coefficients (/ D'/ and r2) between SREBP-2 polymorphisms. C. Haplotypes and their frequencies between two linked SNPs, rs2269657 and rs1052717, in a LD block.
Mentions: To investigate the association of SREBP-2 gene polymorphisms with AVN, we selected four intronic SNPs, rs2267439, rs2269657, rs1052717 and rs2267443, from public databases by considering their allele frequencies and positions, and analyzed these polymorphisms in 443 AVN patients and 273 control subjects. LD coefficients (/D'/) and r2 were calculated, and rs2269657 and rs1052717 demonstrated tight LD (Fig. 1A and 1B). The haplotypes and their frequencies in the LD block between rs2269657 and rs1052717 are showed in Figure 1C.

Bottom Line: SREBP-2 plays a central role in the maintenance of lipid homeostasis through stimulating expression of genes associated with cholesterol biosynthetic pathways.In contrast, rs1052717 and rs2267443 polymorphisms were significantly associated with AVN risk.This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2 Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea. archion@knu.ac.kr

ABSTRACT

Background: It is known that steroid usage and alcohol abuse are major etiological factors in the development of avascular necrosis (AVN), a bone disease that produces osteonecrosis of the femoral head. The facilitation of fat biosynthesis by steroids and alcohol disrupts the blood supply into the femoral head. SREBP-2 plays a central role in the maintenance of lipid homeostasis through stimulating expression of genes associated with cholesterol biosynthetic pathways. The aim of this study was to examine the association between the polymorphisms of the SREBP-2 gene and AVN susceptibility in the Korean population.

Methods: Four single nucleotide polymorphisms (SNP) in the SREBP-2 gene, IVS1+8408 T>C (rs2267439), IVS3-342 G>T (rs2269657), IVS11+414 G>A (rs1052717) and IVS12-1667 G>A (rs2267443), were selected from public databases and genotyped in 443 AVN patients and 273 control subjects by using single-based extension (SBE) genotyping.

Results: The minor allele (C) frequency of rs2267439 showed a significant protective effect on AVN (P = 0.01, OR; 0.75, 95% CI; 0.604-0.935), and the genotype frequencies of this polymorphism were also different from the controls in all alternative analysis models (P range, 0.009-0.03, OR; 0.647-0.744). In contrast, rs1052717 and rs2267443 polymorphisms were significantly associated with AVN risk. Further analysis based on pathological etiology showed that the genotypes of rs2267439, rs1052717 and rs2267443 were also significantly associated with AVN susceptibility in each subgroup.

Conclusion: This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.

Show MeSH
Related in: MedlinePlus