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心肌梗死患者中的脱碘酶、有机阴离子转运多肽多态性与甲状腺激素

Deiodinases, Organic Anion Transporter Polypeptide Polymorphisms, and Thyroid Hormones in Patients with Myocardial Infarction.

作者信息

Brozaitiene Julija, Skiriute Daina, Burkauskas Julius, Podlipskyte Aurelija, Jankauskiene Edita, Serretti Alessandro, Mickuviene Narseta

机构信息

1 Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences , Palanga, Lithuania .

2 Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences , Kaunas, Lithuania .

出版信息

Genet Test Mol Biomarkers. 2018 Apr;22(4):270-278. doi: 10.1089/gtmb.2017.0283. Epub 2018 Mar 20.

Abstract

AIM

To investigate the association among deiodinases (DIO), organic anion-transporting polypeptide 1C1 (OATP1C1) gene polymorphisms, and thyroid hormones (THs) in patients with acute myocardial infarction (AMI).

METHODS

In summary, 290 patients with AMI were evaluated for sociodemographic and clinical characteristics, coronary artery disease (CAD) risk factors, and comorbidities, as well as circulating thyroid-stimulating hormone and TH (triiodothyronine [T3], thyroxine [T4], free T3, free T4, and reverse T3) levels. Ten single nucleotide polymorphisms for thyroid axis related genes: DIO1 (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), DIO2 (rs225014-T/C, rs225015-G/A), DIO3 (rs945006-T/G), and OATP1C1 (rs10444412-T/C, rs10770704-C/T, rs1515777-A/G, rs974453-G/A) were genotyped.

RESULTS

Marginal associations were observed between the DIO1, DIO2, and OATP1C1 gene polymorphisms and almost all analyzed THs (p's < 0.05). After controlling for potential confounders, the OATP1C1 rs1515777-A/G minor allele homozygous genotype (G/G) was associated with a decrease in circulating free T3 and free T3/free T4. In the AMI cohort, associations between: DIO1 rs12095080 and hypertension; DIO2 rs225015 and diabetes mellitus; and the OATP1C1 rs974453 genotype, and AMI type were established.

CONCLUSIONS

DIO1 and DIO2 gene polymorphisms are mainly associated with T3, free T4, free T3/free T4, and [natural-log transformed (ln)] reverse T3 levels, while the OATP1C1 minor allele homozygous genotype is associated with free T3 and free T3/free T4 in CAD patients after AMI.

摘要

目的

探讨急性心肌梗死(AMI)患者中脱碘酶(DIO)、有机阴离子转运多肽1C1(OATP1C1)基因多态性与甲状腺激素(THs)之间的关联。

方法

总共对290例AMI患者进行了社会人口统计学和临床特征、冠状动脉疾病(CAD)危险因素及合并症评估,同时检测了循环甲状腺刺激激素及TH(三碘甲状腺原氨酸[T3]、甲状腺素[T4]、游离T3、游离T4及反式T3)水平。对甲状腺轴相关基因的10个单核苷酸多态性进行基因分型,这些基因包括:DIO1(rs11206244 - C/T、rs12095080 - A/G、rs2235544 - A/C)、DIO2(rs225014 - T/C、rs225015 - G/A)、DIO3(rs945006 - T/G)以及OATP1C1(rs10444412 - T/C、rs10770704 - C/T、rs1515777 - A/G、rs974453 - G/A)。

结果

观察到DIO1、DIO2及OATP1C1基因多态性与几乎所有分析的THs之间存在边缘关联(p值<0.05)。在控制潜在混杂因素后,OATP1C1 rs1515777 - A/G次要等位基因纯合基因型(G/G)与循环游离T3及游离T3/游离T4降低相关。在AMI队列中,确立了DIO1 rs12095080与高血压、DIO2 rs225015与糖尿病以及OATP1C1 rs974453基因型与AMI类型之间的关联。

结论

DIO1和DIO2基因多态性主要与T3、游离T4、游离T3/游离T4及[自然对数转换(ln)]反式T3水平相关,而OATP1C1次要等位基因纯合基因型与AMI后CAD患者的游离T3及游离T3/游离T4相关。

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