Variation in OSBPL10 is associated with dyslipidemia
Variation in OSBPL10 is associated with dyslipidemia
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DOI：
10.1038/hr.2010.28
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发表时间：
2010-05
影响因子：
5.4
通讯作者：
H. Koriyama;H. Nakagami;T. Katsuya;H. Akasaka;S. Saitoh;K. Shimamoto;T. Ogihara;Y. Kaneda;R. Morishita;H. Rakugi
中科院分区：
文献类型：
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作者：
H. Koriyama;H. Nakagami;T. Katsuya;H. Akasaka;S. Saitoh;K. Shimamoto;T. Ogihara;Y. Kaneda;R. Morishita;H. Rakugi
胆固醇稳态的氧固醇假说指出，氧固醇介导胆固醇生物合成的反馈调节。氧固醇结合蛋白参与脂质合成和代谢的控制。在日本个体的全基因组病例对照关联研究中，我们发现具有最小P值的三个单核苷酸多态性（SNP）位于氧固醇结合蛋白样10（OSBPL 10）基因的第五内含子区域。在这项研究中，我们研究了在Tanno和Sobetsu研究中OSBPL 10基因多态性和代谢综合征的危险因素之间的关联。我们选择了四个SNP，包括内含子5中的三个非编码SNP和外显子6中的编码SNP（D254 N）。多态性的基因型频率满足Hardy-Weinberg平衡条件。我们发现，具有rs 2290532（D254 N）多态性的个体的低密度脂蛋白（LDL）胆固醇在CC+ CT基因型受试者中显著高于TT基因型受试者（124.3±1.3 vs. 111.6±4.1 mg/100 ml，P= 0.009）。然而，在收缩压或舒张压、高密度脂蛋白胆固醇或甘油三酯水平方面没有显著差异。多元回归分析显示，rs 2290532（D254 N）与LDL胆固醇相关，与年龄、性别或体重指数无关。两组中基因型频率的比较表明，与低风险（TT）相关的基因型显著降低了高LDL胆固醇血症的风险（P= 0.003），比值比为0.35（95%置信区间= 0.17-0.76）。总体而言，OSBPL 10中的rs 2290532（D254 N）多态性可能使具有该SNP的个体易患高LDL胆固醇血症。
The oxysterol hypothesis of cholesterol homeostasis states that oxysterol mediates feedback regulation of cholesterol biosynthesis. Oxysterol-binding proteins have been implicated in the control of lipid synthesis and metabolism. In a genome-wide case–control association study in Japanese individuals, we found that the three single-nucleotide polymorphisms (SNPs) with the smallest P-values were located in the fifth intronic region of the oxysterol-binding protein-like 10 (OSBPL10) gene. In this study, we examined the association between polymorphisms in the OSBPL10 gene and risk factors for the metabolic syndrome in the Tanno and Sobetsu Study. We selected four SNPs, including three non-coding SNPs in intron 5 and a coding SNP (D254N) in exon 6. Genotype frequencies of the polymorphisms satisfied the conditions for Hardy–Weinberg equilibrium. We found that the low-density lipoprotein (LDL) cholesterol of individuals with the rs2290532 (D254N) polymorphism was significantly greater in subjects with the CC+ CT genotype than in subjects with the TT genotype (124.3±1.3 vs. 111.6±4.1 mg per 100 ml, P= 0.009). However, there were no significant differences in systolic or diastolic blood pressure, high-density lipoprotein cholesterol or triglyceride levels. Multiple regression analysis showed that rs2290532 (D254N) was associated with LDL cholesterol independent of age, sex or body mass index. Comparison of the genotype frequency in both groups indicated that the genotype associated with low risk (TT) reduced the risk of hyper-LDL cholesterolemia significantly (P= 0.003), with an odds ratio of 0.35 (95% confidence interval= 0.17–0.76). Overall, the rs2290532 (D254N) polymorphism in OSBPL10 may predispose individuals with this SNP to hyper-LDL cholesterolemia.