基质金属蛋白酶-2基因多态性与2型糖尿病易感性的关联：一项病例对照研究。

Association of matrix metalloproteinase-2 gene polymorphisms with susceptibility to type 2 diabetes: A case control study.

作者信息

Sarray Sameh, Dallel Meriem, Lamine Laila Ben, Jairajpuri Deeba, Sellami Nejla, Turki Amira, Malalla Zainab, Brock Roland, Ghorbel Mohamed, Mahjoub Touhami

机构信息

Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain; Faculty of Sciences, University Tunis EL Manar, 2092 Manar II, Tunisia.

Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia.

出版信息

J Diabetes Complications. 2021 Jun;35(6):107908. doi: 10.1016/j.jdiacomp.2021.107908. Epub 2021 Mar 16.

DOI:10.1016/j.jdiacomp.2021.107908

PMID:33766491

Abstract

AIMS

Genetic variations mediating MMP-2 expression may result in individual differences in susceptibility to particular diseases. Our aim was to investigate the possible association of certain MMP-2 gene variants with the susceptibility of type 2 diabetes (T2D) in a Tunisian population.

SUBJECTS AND METHODS

A retrospective case-control study involving 310 normoglycemic control subjects and 791 T2D patients was conducted. Genotyping of MMP-2 variants was performed by real time PCR.

RESULTS

Minor allele frequencies (MAF) of the rs243865 and the rs243866 MMP-2, were significantly different between T2D cases and controls. Setting homozygous wild-type genotype carrier as reference, a reduced risk of T2D was seen with the rs243865 and the rs243866 genotypes. Haploview analysis revealed limited linkage disequilibrium between the tested MMP-2 and variants, with most haplotypes (99.5%) captured by 7 MMP-2 haplotypes. Taking the GCCC haplotype as reference for MMP-2 (OR = 1.00), a reduced frequency of TTCC haplotypes (P = 0.04) and the GTCC haplotype (P = 3.5 · 10) was noted in T2D which indicates a protective nature of these two haplotypes for T2D development.

CONCLUSION

To the best of our knowledge, the present study is the first to demonstrate a consistent association of the rs243865 and rs243866 genotype with a protection for T2D.

摘要

目的

介导基质金属蛋白酶-2（MMP-2）表达的基因变异可能导致个体对特定疾病易感性的差异。我们的目的是在突尼斯人群中研究某些MMP-2基因变异与2型糖尿病（T2D）易感性之间的可能关联。

对象与方法

进行了一项回顾性病例对照研究，纳入310名血糖正常的对照者和791名T2D患者。通过实时聚合酶链反应对MMP-2变异进行基因分型。

结果

T2D病例组和对照组之间，MMP-2的rs243865和rs243866的次要等位基因频率（MAF）存在显著差异。以纯合野生型基因型携带者为参照，rs243865和rs243866基因型的T2D风险降低。Haploview分析显示，所检测的MMP-2与变异之间的连锁不平衡有限，7种MMP-2单倍型捕获了大多数单倍型（99.5%）。以MMP-2的GCCC单倍型为参照（OR = 1.00），在T2D中观察到TTCC单倍型（P = 0.04）和GTCC单倍型（P = 3.5·10）的频率降低，这表明这两种单倍型对T2D发展具有保护作用。