Kim Tae-Ho, Baek Jeong-In, Hong Jung Min, Choi Su-Jin, Lee Hye-Jin, Cho Hyun-Ju, Park Eui Kyun, Kim Un-Kyung, Kim Shin-Yoon
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2 Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea.
BMC Med Genet. 2008 Oct 27;9:94. doi: 10.1186/1471-2350-9-94.
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.
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.
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.
This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.
已知类固醇使用和酒精滥用是无血管性坏死（AVN）发展的主要病因，AVN是一种导致股骨头骨坏死的骨病。类固醇和酒精促进脂肪生物合成，破坏了股骨头的血液供应。SREBP - 2通过刺激与胆固醇生物合成途径相关的基因表达，在维持脂质稳态中起核心作用。本研究的目的是检测韩国人群中SREBP - 2基因多态性与AVN易感性之间的关联。
从公共数据库中选择SREBP - 2基因的四个单核苷酸多态性（SNP），即IVS1 + 8408 T>C（rs2267439）、IVS3 - 342 G>T（rs2269657）、IVS11 + 414 G>A（rs1052717）和IVS12 - 1667 G>A（rs2267443），并通过单碱基延伸（SBE）基因分型对443例AVN患者和273例对照受试者进行基因分型。
rs2267439的次要等位基因（C）频率对AVN显示出显著的保护作用（P = 0.01，OR；0.75，95% CI；0.604 - 0.935），并且在所有替代分析模型中，该多态性的基因型频率也与对照组不同（P范围，0.009 - 0.03，OR；0.647 - 0.744）。相反，rs1052717和rs2267443多态性与AVN风险显著相关。基于病理病因的进一步分析表明，rs2267439、rs1052717和rs2267443的基因型在每个亚组中也与AVN易感性显著相关。
本研究是评估韩国人群中SREBP - 2基因多态性与AVN易感性之间关联的首次报道。
