Dataset Information

MMP2 rs243866 and rs2285053 Polymorphisms and Alzheimer's Disease Risk in Slovak Caucasian Population.

ABSTRACT: Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by progressive loss of memory. In the AD brain, matrix metalloproteinases (MMPs) are involved in the disruption of the blood-brain barrier resulting in a neuroinflammatory response. The objective of our investigation was to assess the association of MMP2 rs243866 and rs2285053 polymorphisms with susceptibility to AD, to assess the interaction of MMP2 variants with APOE ε4 risk allele, and to evaluate their influence on the age at disease onset and MoCA score. A total of 215 late-onset AD patients and 373 control subjects from Slovakia were genotyped for MMP2 rs243866 and rs2285053 polymorphisms. The MMP2 association with AD risk and clinical parameters was evaluated by logistic and linear regression analyses. No statistically significant differences in either MMP2 rs243866 and rs2285053 allele or genotype frequencies between AD patients and the control group have been observed (p > 0.05). However, the correlation with clinical findings revealed a higher age at disease onset in MMP2 rs243866 GG carriers in the dominant model as compared to other MMP2 genotype carriers (p = 0.024). Our results suggest that MMP2 rs243866 promoter polymorphism may have an impact on the age at AD onset in the patients.

SUBMITTER: Ocenasova A

PROVIDER: S-EPMC10143987 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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MMP2 rs243866 and rs2285053 Polymorphisms and Alzheimer's Disease Risk in Slovak Caucasian Population.

Ocenasova Agata A Shawkatova Ivana I Javor Juraj J Parnicka Zuzana Z Minarik Gabriel G Kralova Maria M Kiralyova Iliana I Mikolaskova Iveta I Durmanova Vladimira V

Life (Basel, Switzerland) 20230326 4

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by progressive loss of memory. In the AD brain, matrix metalloproteinases (MMPs) are involved in the disruption of the blood-brain barrier resulting in a neuroinflammatory response. The objective of our investigation was to assess the association of MMP2 rs243866 and rs2285053 polymorphisms with susceptibility to AD, to assess the interaction of MMP2 variants with APOE ε4 risk allele, and to ...[more]

PMID: 37109410

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Project description:INTRODUCTION: DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMTs). In cancer cells, global hypomethylation of the genome as a whole and regional hypermethylation of CpG islands have been reported. Four groups of DNMTs have been identified: DNMT1, DNMT2 (TRDMT1), DNMT3A and DNMT3B. DNMT2 uses the catalytic mechanism of DNMTs, but does in fact methylate RNA. Little is known about the significance of these genes in human breast cancer. In the study presented herein, we analyzed five distinct DNMT single SNPs with regard to potential associations with breast cancer risk. CASE DESCRIPTION: In this study, we genotyped 221 female Caucasian breast cancer patients and 221 female Caucasian healthy controls, and we used five allele-specific real-time polymerase chain reaction (qPCR) assays. We selected one locus within the DNMT1 gene and two loci within the DNMT3A and DNMT3B genes, respectively. Statistics were calculated using the chi-squared and Fisher's exact tests, and correlated with clinical parameters such as age, diagnosis, histology, TNM stage, hormonal receptor status, human epidermal growth factor receptor 2 (HER2) status, response to treatment and survival. Statistically significant results were obtained for correlations with the DNMT1 gene. DISCUSSION AND EVALUATION: Five genomic loci within the DNMT1, DNMT3A and DNMT3B genes were assessed. Statistical significance (P = 0.030) was identified for DNMT1 SNP (A201G, rs2228612): six women within the control group were GG homozygous (variant), while this mutation was absent in the breast cancer group. CONCLUSIONS: We conclude that women with the DNMT1 SNP (A201G, rs2228612) GG homozygous genotype (variant) have a lower risk of developing breast cancer compared to heterozygous or wildtype genotypes. To date, alterations within the DNMT1 gene have not been reported to be associated with cancer in the Caucasian population.

Project description:AimsDilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc-dependent and calcium-containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population.Methods and resultsA total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865-C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P < 0.05). Besides, rs243865-C allele presented a correlation with the poor prognosis of DCM patients in both dominant (HR = 2.0, 95% confidence interval [CI] = 1.14-3.57, P = 0.017) and additive (HR = 1.85, 95% CI = 1.09-3.13, P = 0.02) model. The statistical significance remained after adjustment for sex, age, hypertension, diabetes, hyperlipidaemia, and smoking status. There were significant differences in left ventricular end-diastolic diameter and left ventricular ejection fraction between rs243865-CC and CT genotypes. Functional analysis indicated that rs243865-C allele increased luciferase activity and the mRNA expression level of MMP2 by facilitating ZNF354C binding.ConclusionsOur study suggested that MMP2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese Han population.

Project description:The role of vitamin D in Alzheimer's Disease (AD) has been studied over the past years. The results from numerous studies have indicated that the molecular pathways involved in the development of AD are closely related to the molecular pathways of the mechanisms of action of vitamin D. However, only a limited number of studies have described the key role of vitamin D receptor (VDR) in the regulation of the functions of vitamin D and the potential effect of single nucleotide polymorphisms (SNPs) of the VDR gene. Thus, the aim of the present study was to investigate the VDR TaqI polymorphism in relation to AD in a Southeastern European Caucasian (SEC) cohort. Further, the present study aimed to compare the results obtained with those of other AD populations. For this purpose, blood samples from 90 confirmed patients with AD [median age, 74 years; median mini-mental state examination (MMSE) score of 21; median frontal assessment battery (FAB) score of 10] and 103 healthy controls (median age, 57 years) were analyzed to determine the genotypes of TaqI (rs731236) using quantitative PCR. The frequencies (%) of the TaqI TT, TC and CC genotypes in the controls/patients were 34/48.9, 47.6/41.1 and 18.4/10.0, respectively. Statistically significant differences were observed for the TaqI C allele [odds ratio (OR). 0.54; 95% confidence interval (CI), 0.30-0.96; P=0.035], the TaqI TT genotype (OR, 1.86; 95% CI, 1.04-3.32; P=0.035) and the TaqI CC genotype (OR, 0.119; 95% CI, 0.014-0.995; P=0.032,) in relation to the MMSE score <21 in the patient's group. The TaqI TT allele was found to increase the risk of developing AD by 1.86-fold in the SEC population, while the TaqI C allele may act protectively, with a 46% lower risk of developing the disease. Patients with the TaqI CC genotype were found to have an 88% less likelihood of developing severe cognitive impairment based on the MMSE score. On the whole, the present study did not confirm the results of previous studies on the VDR TaqI C allele in patients with AD.

Project description:Vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been investigated over the past years with the aim of identifying any association with the development of Alzheimer's disease (AD). However, information regarding the potential association of VDR SNP haplotypes with AD is limited. The aim of the present study was to provide additional knowledge on the effects of VDR haplotypes on the development of late-onset AD in a cohort of Southeastern European Caucasians (SECs). The study sample included 78 patients with late-onset AD and 103 healthy subjects as the control group. VDR SNPs that were analyzed were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing the disease (OR, 0.47; 95% CI, 0.23-0.96; P=0.04) and the TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6-fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91-20.13; P=0.0028). Female subjects carrying the TAC haplotype had a ~9-fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86-46.28; P<0.05). The TaqI and BsmI polymorphisms were in high linkage disequilibrium (D'=0.9717, r=0.8467) and produced a haplotype with a statistically significant different frequency between the control and AD group. The TA (TaqI and BsmI) haplotype was associated with an ~8-fold greater risk of developing AD (OR, 8.27; 95% CI, 2.70-25.28; P<0.05). Female TA carriers had an ~14-fold greater risk of developing the disease in comparison to female control subjects (OR, 13.93; 95% CI, 2.95-65.87; P<0.05). On the whole, the present study demonstrates that in the SEC population, TAC and TA are risk haplotypes for AD, while the CAC haplotype may act protectively. SEC women carrying the TAC or TA haplotype are at a greater risk of developing AD, thus suggesting that women are markedly affected by the poor utilization of vitamin D induced by the VDR haplotype.

Dataset Information

MMP2 rs243866 and rs2285053 Polymorphisms and Alzheimer's Disease Risk in Slovak Caucasian Population.

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<i>MMP2</i> rs243866 and rs2285053 Polymorphisms and Alzheimer's Disease Risk in Slovak Caucasian Population.

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