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胰岛素抵抗和肥胖候选基因中的常见多态性对病态肥胖受试者在腹腔镜可调节胃束带术和低热量饮食后体重减轻的影响。

Impact of common polymorphisms in candidate genes for insulin resistance and obesity on weight loss of morbidly obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet.

作者信息

Sesti Giorgio, Perego Lucia, Cardellini Marina, Andreozzi Francesco, Ricasoli Cristina, Vedani Paola, Guzzi Valeria, Marchi Monica, Paganelli Michele, Ferla Gianfranco, Pontiroli Antonio E, Hribal Marta Letizia, Folli Franco

机构信息

Dipartimento Medicina Sperimentale e Clinica, Università Magna-Graecia di Catanzaro, Via Campanella, 115, 88100 Catanzaro, Italy.

出版信息

J Clin Endocrinol Metab. 2005 Sep;90(9):5064-9. doi: 10.1210/jc.2005-0404. Epub 2005 Jun 28.

DOI:10.1210/jc.2005-0404
PMID:15985484
Abstract

CONTEXT

It is unknown whether genetic factors that play an important role in body weight homeostasis influence the response to laparoscopic adjustable gastric banding (LAGB).

OBJECTIVE

We investigated the impact of common polymorphisms in four candidate genes for insulin resistance on weight loss after LAGB.

DESIGN

The design was a 6-month follow-up study.

SETTING

The study setting was hospitalized care.

PATIENTS

A total of 167 unrelated morbidly obese subjects were recruited according to the following criteria: age, 18-66 yr inclusive; and body mass index greater than 40 kg/m2 or greater than 35.0 kg/m2 in the presence of comorbidities.

INTERVENTION

LAGB was used as an intervention.

MAIN OUTCOME MEASURE

Measure of correlation between weight loss and common polymorphisms in candidate genes for insulin resistance and obesity was the main outcome measure.

RESULTS

The following single nucleotide polymorphisms were detected by digestion of PCR products with appropriate restriction enzymes: Gly972Arg of the insulin receptor substrate-1 gene, Pro12Ala of the proliferator-activated receptor-gamma gene, C-174G in the promoter of IL-6 gene, and G-866A in the promoter of uncoupling protein 2 gene. Baseline characteristics including body mass index did not differ between the genotypes. At the 6-month follow-up after LAGB, carriers of G-174G IL-6 genotype had lost more weight than G-174C or C-174C genotype (P = 0.037), and carriers of A-866A uncoupling protein 2 genotype had lost more weight as compared with G-866G (P = 0.018) and G-866A (P = 0.035) genotype, respectively. Weight loss was lower in carriers of Gly972Arg insulin receptor substrate-1 genotype than Gly972Gly carriers, but not statistically significant (P = 0.06). No difference between carriers of Pro12Ala and Pro12Pro proliferator-activated receptor-gamma genotype was observed.

CONCLUSIONS

These data demonstrate that genetic factors, which play an important role in the regulation of body weight, may account for differences in the therapeutic response to LAGB.

摘要

背景

在体重稳态中起重要作用的遗传因素是否会影响腹腔镜可调节胃束带术(LAGB)的疗效尚不清楚。

目的

我们研究了胰岛素抵抗的四个候选基因中的常见多态性对LAGB术后体重减轻的影响。

设计

该设计为一项为期6个月的随访研究。

地点

研究地点为住院治疗。

患者

共招募了167名无亲缘关系的病态肥胖受试者,入选标准如下:年龄在18至66岁之间;体重指数大于40kg/m²,或在合并症存在的情况下大于35.0kg/m²。

干预措施

采用LAGB作为干预手段。

主要观察指标

体重减轻与胰岛素抵抗和肥胖候选基因常见多态性之间的相关性测量是主要观察指标。

结果

通过用适当的限制性内切酶消化PCR产物检测到以下单核苷酸多态性:胰岛素受体底物-1基因的Gly972Arg、增殖激活受体-γ基因的Pro12Ala、IL-6基因启动子中的C-174G以及解偶联蛋白2基因启动子中的G-866A。各基因型之间包括体重指数在内的基线特征无差异。在LAGB术后6个月的随访中,IL-6基因G-174G基因型携带者比G-174C或C-174C基因型携带者体重减轻更多(P = 0.037),解偶联蛋白2基因A-866A基因型携带者分别比G-866G(P = 0.018)和G-866A(P = 0.035)基因型携带者体重减轻更多。胰岛素受体底物-1基因Gly972Arg基因型携带者的体重减轻低于Gly972Gly携带者,但差异无统计学意义(P = 0.06)。未观察到增殖激活受体-γ基因Pro12Ala和Pro12Pro基因型携带者之间存在差异。

结论

这些数据表明,在体重调节中起重要作用的遗传因素可能是LAGB治疗反应差异的原因。

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