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OLR1基因的IVS4单核苷酸多态性与冠状动脉疾病有关吗:IVS4单核苷酸多态性之间存在连锁关系吗?

Are IVS4 SNPs of OLR1 gene associated with coronary artery disease: Is there a linkage between IVS4 SNPs?

作者信息

Kurnaz-Gomleksiz Ozlem, Kucukhuseyin Ozlem, Ozkok Elif, Bugra Zehra, Ozturk Oguz, Yilmaz-Aydogan Hulya

机构信息

Department of Molecular Medicine, Institute for Experimental Medicine, Istanbul University, Turkey.

Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Turkey.

出版信息

Adv Clin Exp Med. 2018 Mar;27(3):321-326. doi: 10.17219/acem/68395.

Abstract

BACKGROUND

The OLR1 gene has been identified as a candidate gene for coronary artery disease (CAD). Six single-nucleotide polymorphisms (SNPs) of the OLR1 gene located within intron 4 (IVS4-27G>C, IVS4-73C>T, IVS4-14A>G), intron 5 (IVS5-70A>G, IVS5-27G>T) and 3'UTR (188C>T) comprise a linkage disequilibrium (LD) block, which is strongly associated with the elevated risk of CAD.

OBJECTIVES

We aimed to investigate the effects of the OLR1 IVS4-14A>G and -73C>T SNPs on metabolic parameters in Turkish CAD patients, and the linkage between these 2 genetic variants.

MATERIAL AND METHODS

The present study was carried out in 97 CAD patients and 78 healthy individuals. The OLR1 IVS4 genotypings were performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method.

RESULTS

Serum high-density lipoprotein (HDL) cholesterol levels and body mass index (BMI) were higher in control subjects with IVS4-73CC genotype than in T allele carriers (CT+TT) (respectively, p = 0.002 and p = 0.024), while BMI values were lower in patients with CC genotype (p = 0.046). Patients with IVS4-14G allele (AG+GG) had a statistically higher low-density lipoprotein (LDL) cholesterol level (p = 0.027) than patients with -14AA genotype. Also the systolic blood pressure (SBP) levels were statistically higher in IVS4- 73C allele carriers (CT+CC) than in non-carriers (TT) (p = 0.045). A strong linkage between IVS4-14A>G and -73C>T SNPs of the OLR1 gene was detected in patients (D > 0.76).

CONCLUSIONS

Our results indicated that the intron 4-14A>G and -73C>T SNPs of the OLR1 gene can be inherited together. The present data also suggests that the OLR1 gene may contribute to the development of hypercholesterolemia in patients with CAD.

摘要

背景

OLR1基因已被确定为冠状动脉疾病(CAD)的候选基因。位于第4内含子(IVS4-27G>C、IVS4-73C>T、IVS4-14A>G)、第5内含子(IVS5-70A>G、IVS5-27G>T)和3'非翻译区(188C>T)的OLR1基因的6个单核苷酸多态性(SNP)构成一个连锁不平衡(LD)块,与CAD风险升高密切相关。

目的

我们旨在研究OLR1基因IVS4-14A>G和-73C>T单核苷酸多态性对土耳其CAD患者代谢参数的影响,以及这两种基因变异之间的连锁关系。

材料与方法

本研究纳入97例CAD患者和78例健康个体。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对OLR1基因IVS4进行基因分型。

结果

IVS4-73CC基因型的对照组血清高密度脂蛋白(HDL)胆固醇水平和体重指数(BMI)高于T等位基因携带者(CT+TT)(分别为p = 0.002和p = 0.024),而CC基因型患者的BMI值较低(p = 0.046)。IVS4-14G等位基因(AG+GG)的患者低密度脂蛋白(LDL)胆固醇水平在统计学上高于-14AA基因型患者(p = 0.027)。此外,IVS4-73C等位基因携带者(CT+CC)的收缩压(SBP)水平在统计学上高于非携带者(TT)(p = 0.045)。在患者中检测到OLR1基因IVS4-14A>G和-73C>T单核苷酸多态性之间存在强连锁关系(D>0.76)。

结论

我们的结果表明,OLR1基因第4内含子-14A>G和-73C>T单核苷酸多态性可能共同遗传。目前的数据还表明,OLR1基因可能在CAD患者高胆固醇血症的发生中起作用。

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