Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia

Minyaylo, Oksana; Ponomarenko, Irina; Reshetnikov, Evgeny; Dvornyk, Volodymyr; Churnosov, Mikhail

doi:10.1038/s41598-021-92527-y

Cited by 33 publications

(21 citation statements)

References 48 publications

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“…Ten polymorphic loci of the five MMP genes, such as c.-1607 2G > 1G (rs1799750) MMP1 , c.-1306 C > T (rs243865) MMP2 , c.133 C > T (rs679620) MMP3 , c.259 T > C (rs1940475) MMP8 , c.-1562 C > T (rs3918242) MMP9 , c.139-369 T > C (rs3918249) MMP9 , c.836 A > G (rs17576) MMP9 , c. 1331-163 G > A (rs3787268) MMP9 , c. 1721 C > G (rs2250889) MMP9 , and c.2003 G > A (rs17577) MMP9 were selected from previous BC association studies ( Supplementary Table S1 ) [ 13 , 14 , 15 , 16 ], etc., and the assessment of their functional value ( Supplementary Table S2 ) [ 26 , 27 , 29 , 35 , 36 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

et al. 2022

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Objective: We investigated the possible modifying effect of obesity on the association of matrix metalloproteinase (MMP) gene polymorphisms with breast cancer (BC) risk. Methods: A total of 1104 women divided into two groups according to their body mass index (BMI): BMI ≥ 30 (119 BC, and 190 control) and BMI < 30 (239 BC, and 556 control) were genotyped for specially selected (according to their association with BC in the previous study) 10 single-nucleotide polymorphisms (SNP) of MMP1, 2, 3, 8, and 9 genes. Logistic regression association analysis was performed in each studied group of women (with/without obesity). Functional annotation of BC-correlated MMP polymorphic variants was analyzed by in silico bioinformatics. Results: We observed significant differences in the involvement of MMP SNPs in BC in obese and non-obese women. Polymorphic loci MMP9 (c.836 A > G (rs17576) and c. 1721 C > G (rs2250889)) were BC-protective factors in obese women (OR 0.71, allelic model, and OR 0.55, additive model, respectively). Genotypes TT MMP2 (c.-1306 C > T,rs243865) and AA MMP9 (c. 1331-163 G > A,rs3787268) determined BC susceptibility in non-obese women (OR 0.31, and OR 2.36, respectively). We found in silico substantial multidirectional influences on gene expression in adipose tissue BC-related polymorphic loci: BC risk allele A-rs3787268 in non-obese women is associated with low expression NEURL2, PLTP, RP3-337O18.9, SPATA25, and ZSWIM1, whereas BC risk allele A-rs17576 in obese women is associated with high expression in the same genes in visceral and/or subcutaneous adipose. Conclusions: our study indicated that obesity has a significant modifying effect on the association of MMP genes with BC risk in postmenopausal women.

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Section: Methodsmentioning

confidence: 99%

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

et al. 2022

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“…MMP gene SNPs associated with BC reported in more than 50 previous association studies [ 12 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] ( Supplementary Table S15 ) and with potential regulatory functions ( Supplementary Table S16 ) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ] were selected for our genetic–epidemiological study. As a result, 10 SNPs of the MMP genes were investigated in this study, including 6 loci of chromosome 20 (c.139-369 T > C (rs3918249) MMP9 , c. 1331-163 G > A (rs3787268) MMP9 , c.2003 G > A (rs17577) MMP9 , c.-1562 C > T (rs3918242) MMP9 , c.836 A > G (rs17576) MMP9 , c. 1721 C > G (rs2250889) MMP9 ), 3 SNP of chromosome 11 (c.259 T > C (rs1940475) MMP8 , c.133 C > T (rs679620) MMP3 , c.-1607 2G > 1G (rs1799750) MMP1 ), and 1 locus of chromosome 16 (c.-1306 C > T (rs243865) MMP2 ).…”

Section: Methodsmentioning

confidence: 99%

Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia

Pavlova

Demin

Churnosov

et al. 2022

IJMS

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We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From BC-related genes in previous studies, ten single nucleotide polymorphisms (SNPs) in five MMP genes (MMP1, 2, 3, 8, 9) were genotyped. The BC risk was calculated by logistic regression (to evaluate the SNPs’ independent effects) and model-based multifactor dimensionality reduction (MB-MDR) (to identify SNP–SNP interactions) methods. The allelic variants’ distribution of c.836 A>G (rs17576) and c. 1721 C>G (rs2250889) MMP9 was significantly different between BC and cancer-free women: for G minor alleles, these SNPs manifested disorder protective effects (OR 0.82 and OR 0.67–0.71, respectively, pperm ≤ 0.035). Eleven haplotypes of six SNPs MMP9 were involved in BC risk (nine haplotypes) and protective (two haplotypes) effects. All 10 SNPs of the MMP genes examined were associated with BC within the 13 SNP–SNP interaction simulated models, with a pivotal role of the two-locus (rs17577 × rs3918242) MMP9 epistatic interaction (defined as 1.81% BC entropy within more than 60% of the genetic models). Under in silico bioinformatics, BC susceptibility MMP polymorphic loci are located in functionally active genome regions and impact genes expression and splicing “regulators” in the mammary gland. The biological pathways of BC MMP candidate genes are mainly realized due to metalloendopeptidase activity and extracellular matrix organization (structure, disassembly, metabolic process, etc.). In conclusion, our data show that MMP gene polymorphisms are related to BC susceptibility in the Caucasian women of Russia.

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“…To estimate the potential downstream functional effects of the AD-associated variants and their proxies (r 2 ≥0.8) [ 46 , 47 ], we used the available data of epigenetic effects (HaploReg [ 34 ]), non-synonymous functional predictions (SIFT and PolyPhen-2 databases [ 48 , 49 ]), expression and alternative splicing quantitative traits (GTExconsortium atlas, [ 50 ]). HaploReg and European population data of the 1000 Genomes Project Phase 1 were used to identify variants in close linkage disequilibrium (r 2 ≥ 0.8) with the AD-associated variants [ 51 , 52 ].…”

Section: Methodsmentioning

confidence: 99%

Filaggrin gene polymorphisms are associated with atopic dermatitis in women but not in men in the Caucasian population of Central Russia

et al. 2021

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Background and purpose This study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia. Methods The study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females. Results Significant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19–2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18–2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology. Conclusion Polymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia.

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Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia

Cited by 33 publications

References 48 publications

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia

Filaggrin gene polymorphisms are associated with atopic dermatitis in women but not in men in the Caucasian population of Central Russia

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