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对氧磷酶1基因多态性(L55M和Q192R)能否保护1型糖尿病儿童免于脂质异常?

Can paraoxonase 1 polymorphisms (L55 M and Q192 R) protect children with type 1 diabetes against lipid abnormalities?

作者信息

Fekih Ons, Triki Sonia, Hellara Ilhem, Neffati Fadoua, Rejeb Jihen, Ommezzine Asma, Chouchane Slaheddine, Guediche Mohamed Neji, Bouslama Ali, Najjar Mohamed Fadhel

机构信息

Laboratory of Biochemistry and Toxicology, Monastir University Hospital, Monastir 5000, Tunisia.

Laboratory of Biochemistry and Toxicology, Monastir University Hospital, Monastir 5000, Tunisia.

出版信息

J Clin Lipidol. 2014 May-Jun;8(3):249-55. doi: 10.1016/j.jacl.2014.03.001. Epub 2014 Mar 12.

Abstract

BACKGROUND

Only a few studies have focused on the possible modulatory role of paraoxonase 1 (PON1) polymorphisms in lipid profiles, especially in children and in adolescents with type 1 diabetes (T1D).

OBJECTIVE

We propose to study the association between PON1 polymorphisms (PON1-55 and PON1-192) and a lipid profile in a young Tunisian population with T1D.

METHODS

The study compared 122 children and adolescents with T1D with 97 controls. Genomic DNA was collected from 116 patients and 91 controls. Lipid parameters were determined by automated methods. PON1 activity was measured by a spectrophotometric method and genotyping of the PON1 gene was assessed by multiplex polymerase chain reaction followed by restriction fragment-length polymorphism.

RESULTS

A significant increase in total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)) and a significant decrease in apolipoprotein A1 (ApoA1), ApoA1/ApoB ratio, and PON1 activity/HDL-C ratio were observed in children with T1D compared with controls. In the LLQR haplotype, the group with diabetes showed significantly higher values of total cholesterol, LDL-C, apoB, Lp(a), and apoA1/apoB ratio compared with the control group. Those with diabetes with the LLQQ haplotype showed a significant decrease in LDL-C and Lp(a) compared with controls (P < .0001).

CONCLUSION

PON1 polymorphisms (PON1-55 and PON1-192) seem to be involved in the altering the lipid profile in T1D. The LLQR haplotype provided an atherogenic lipid profile in children with T1D compared with controls. LLQQ haplotype seemed to have a protective effect against the increase in LDL-C and Lp(a) that are heavily involved in the development of cardiovascular diseases.

摘要

背景

仅有少数研究关注对氧磷酶1(PON1)基因多态性在血脂谱中的可能调节作用,尤其是在1型糖尿病(T1D)儿童和青少年中。

目的

我们拟研究突尼斯年轻T1D人群中PON1基因多态性(PON1 - 55和PON1 - 192)与血脂谱之间的关联。

方法

该研究将122例T1D儿童和青少年与97例对照进行比较。从116例患者和91例对照中收集基因组DNA。采用自动化方法测定血脂参数。通过分光光度法测量PON1活性,并通过多重聚合酶链反应随后进行限制性片段长度多态性分析评估PON1基因的基因分型。

结果

与对照组相比,T1D儿童的总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇(LDL - C)、载脂蛋白B(ApoB)和脂蛋白(a)(Lp(a))显著升高,而载脂蛋白A1(ApoA1)、ApoA1/ApoB比值和PON1活性/HDL - C比值显著降低。在LLQR单倍型中,糖尿病组的总胆固醇、LDL - C、ApoB、Lp(a)和ApoA1/ApoB比值显著高于对照组。与对照组相比,具有LLQQ单倍型的糖尿病患者的LDL - C和Lp(a)显著降低(P <.0001)。

结论

PON1基因多态性(PON1 - 55和PON1 - 192)似乎参与了T1D患者血脂谱的改变。与对照组相比,LLQR单倍型使T1D儿童呈现致动脉粥样硬化的血脂谱。LLQQ单倍型似乎对LDL - C和Lp(a)的升高具有保护作用,而LDL - C和Lp(a)的升高与心血管疾病的发生密切相关。

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