Combination Of Gene Polymorphisms Research Articles

Secondary risk factors of sudden cardiac death and genes of arterial hypertension

Purpose. To study the influence of polymorphisms of arterial hypertension genes and their various combinations on individual risk factors of sudden cardiac death.
 Materials and methods. 319 young people from 18 to 24 years of age who are entering military service by conscription were examined. The survey identified 69 individuals with signs of increased risk of sudden cardiac death after being examined for secondary risk factors of sudden cardiac death and taken a blood test to determine the polymorphisms of the genes AGT 521 CT, GNB3 825 CT, CYP11B2 344 CT, NOS3 786 TC.
 Results. The greatest influence on the severity of secondary risk factors was exerted by the following variants of a combination of gene polymorphisms: AGT 521 CT and NOS3 786 TC in the individuals with a heterozygous risk variant, both genes showed a significant increase in the duration of the corrected QT interval, heart rate, and a decrease in heart rate variability. AGT 521 CT and CYP11B2 344 CT homozygous risk variant of the CYP11B2 344 CT and the heterozygous risk variant AGT 521 CT is associated with a longer duration of the corrected QT interval, and the heterozygous risk variant for both genes is associated with higher heart rate values. AGT 521 CT and GNB3 825 CT combination of a homozygous risk variant of the gene GNB3 825 CT and the heterozygous variant of the gene AGT 521 CT is associated with the greatest effect on a heart rate.
 Conclusions. The presence of a homozygous risk variant of the gene NOS3 786 TC, a heterozygous risk variant of the gene GNB3 825 CT is prognostically unfavorable for its effect on the severity of secondary risk factors for sudden cardiac death. The combination of the heterozygous variant AGT 521 CT with a heterozygous variant of NOS3 786 TC and a homozygous risk variant by the gene CYP11B2 344 CT and the heterozygous risk variant AGT 521 CT are also the most unfavorable in terms of its effect on secondary risk factors for sudden cardiac death. Secondary risk factors of sudden cardiac death are influenced by both individual polymorphisms of genes of arterial hypertension, and their various combinations.

Serum Level and Genetic Polymorphism of Secretary Phospholipase A2-IIA in Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is a neurodegenerative disease and is the most common because of late life dementia. Alteration of Secretary Phospholipase A2-IIA (sPLA2-IIA) may have an important role in membrane phospholipids metabolism and the pathogenesis of AD. The aim of our study was to determine serum levels and genetic variant of sPLA2-IIA in Alzheimer’s disease and compare to controls. Methods: This study included 40 healthy unrelated individuals and 40 patients with AD. Serum levels and the polymorphisms of sPLA2-IIA enzyme were determined. Results: In Alzheimer patients¸ the CC genotype and C allele frequencies of enzyme were significantly lower while the CG and GG genotypes and G allele frequencies of enzyme were significantly higher than controls. The mean concentration and mean rank of enzyme for CC genotype significantly were lower while the CG and GG genotypes of enzyme were significantly higher than controls. Conclusion: The effect of different gene polymorphisms for the incident of AD is still unclear. We determined gene polymorphisms of sPLA2-IIA which may relate to AD. It can be suggest that a single or combination of gene polymorphisms have possible effect for development of AD. Further studies are needed to research the functional roles of sPLA2-IIA in the context of AD.

Combinations of Polymorphisms in Genes Involved in the 5-Fluorouracil Metabolism Pathway Are Associated with Gastrointestinal Toxicity in Chemotherapy-Treated Colorectal Cancer Patients

The purpose of this study was to investigate whether specific combinations of polymorphisms in genes encoding proteins involved in 5-fluorouracil (5-FU) pharmacokinetics and pharmacodynamics are associated with increased risk of treatment-induced toxicity. We analyzed two cohorts of 161 and 340 patients, the exploration and validation cohort, respectively. All patients were treated similarly with 5-FU-based adjuvant chemotherapy. We analyzed 13 functional polymorphisms and applied a four-fold analysis strategy using individual polymorphisms, haplotypes, and phenotypic enzyme activity or expression classifications based on combinations of functional polymorphisms in specific genes. Furthermore, multifactor dimensionality reduction analysis was used to identify a genetic interaction profile indicating an increased risk of toxicity. Alleles associated with low activity of methylene tetrahydrofolate reductase (MTHFR) were associated with decreased risk of toxicity [OR(Exploration) 0.39 (95% CI: 0.21-0.71, P = 0.003), OR(Validation) 0.63 (95% CI: 0.41-0.95, P = 0.03)]. A specific combination of the MTHFR 1298A>C and thymidylate synthase (TYMS) 3'-UTR (untranslated region) ins/del polymorphisms was significantly associated with increased toxicity in both cohorts [OR(Exploration) 2.40 (95% CI: 1.33-4.29, P = 0.003), OR(Validation) 1.81 (95% CI: 1.18-2.79, P = 0.007)]. The specific combination was also associated with increased cumulative incidence and earlier occurrence of severe toxicity during treatment. Our results indicate that MTHFR activity and a specific combination of the MTHFR 1298A>C and TYMS 3'-UTR ins/del polymorphisms are possible predictors of 5-FU treatment-related toxicity.

Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans

Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology.