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载脂蛋白酯酶和肝脂肪酶基因与 2 型糖尿病风险的相互作用:特内里费研究的结果。

Interaction between cholesteryl ester transfer protein and hepatic lipase encoding genes and the risk of type 2 diabetes: results from the Telde study.

机构信息

Servicio de Endocrinología, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Las Palmas de Gran Canaria, Spain.

出版信息

PLoS One. 2011;6(11):e27208. doi: 10.1371/journal.pone.0027208. Epub 2011 Nov 3.

Abstract

BACKGROUND AND AIM

Diabetic dyslipidaemia is common in type 2 diabetes (T2D) and insulin resistance and often precedes the onset of T2D. The Taq1B polymorphism in CETP (B1 and B2 alleles) (rs708272) and the G-250A polymorphism in LIPC (rs2070895) are associated with changes in enzyme activity and lipid concentrations. Our aim was to assess the effects of both polymorphisms on the risk of T2D.

METHODS AND RESULTS

In a case-control study from the population-based Telde cohort, both polymorphisms were analysed by PCR-based methods. Subjects were classified, according to an oral glucose tolerance test, into diabetic (N = 115) and pre-diabetic (N = 116); 226 subjects with normal glucose tolerance, matched for age and gender, were included as controls. Chi-square (comparison between groups) and logistic regression (identification of independent effects) were used for analysis. The B1B1 Taq1B CETP genotype frequency increased with worsening glucose metabolism (42.5%, 46.1% and 54.3% in control, IGR and diabetic group; p = 0.042). This polymorphism was independently associated with an increased risk of diabetes (OR: 1.828; IC 95%: 1.12-2.99; p = 0.016), even after adjusting by confounding variables, whereas the LIPC polymorphism was not. Regarding the interaction between both polymorphisms, in the B1B1 genotype carriers, the absence of the minor (A) allele of the LIPC polymorphism increased the risk of having diabetes.

CONCLUSION

The presence of the B1B1 Taq1B CETP genotype contributes to the presence of diabetes, independently of age, sex, BMI and waist. However, among carriers of B1B1, the presence of GG genotype of the -250 LIPC polymorphism increases this risk further.

摘要

背景与目的

糖尿病血脂异常在 2 型糖尿病(T2D)和胰岛素抵抗中很常见,并且常常先于 T2D 的发生。CETP 中的 Taq1B 多态性(B1 和 B2 等位基因)(rs708272)和 LIPC 中的 G-250A 多态性(rs2070895)与酶活性和脂质浓度的变化有关。我们的目的是评估这两种多态性对 T2D 发病风险的影响。

方法与结果

在一项基于人群的 Telde 队列的病例对照研究中,我们采用基于 PCR 的方法分析了这两种多态性。根据口服葡萄糖耐量试验,将受试者分为糖尿病(N = 115)和糖尿病前期(N = 116);226 名年龄和性别相匹配的糖耐量正常的受试者被纳入对照组。采用卡方检验(组间比较)和逻辑回归(识别独立影响因素)进行分析。Taq1B CETP 基因型的 B1B1 频率随着葡萄糖代谢的恶化而增加(对照组、IGR 和糖尿病组的频率分别为 42.5%、46.1%和 54.3%;p = 0.042)。该多态性与糖尿病的发病风险增加独立相关(OR:1.828;95%CI:1.12-2.99;p = 0.016),即使在调整混杂变量后也是如此,而 LIPC 多态性则不然。关于这两种多态性之间的相互作用,在 B1B1 基因型携带者中,LIPC 多态性的次要(A)等位基因缺失增加了患糖尿病的风险。

结论

B1B1 Taq1B CETP 基因型的存在独立于年龄、性别、BMI 和腰围,与糖尿病的发生有关。然而,在 B1B1 携带者中,LIPC-250 多态性的 GG 基因型的存在进一步增加了这种风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3067/3207838/df2154626c8b/pone.0027208.g001.jpg

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