Influence Of Gene Polymorphisms Research Articles

Genetic aspects of lone atrial fibrillation in patients without structural heart disease

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Among patients with AF the subgroup posessing AF without traditional risk factors is differentiated. Such patients are commonly referred as having lone AF and comprise 1020% of all cases. A number of studies have demonstrated that the background of AF, and in particular lone AF, have a substantial genetic component.
 Aims: To evaluate the influence of gene polymorphism to the development of atrial fibrillation in patients without concomitant valvular pathology and coronary artery disease.
 Materials and methods: The study included 174 patients with atrial fibrillation and 124 controls without any cardiovascular pathology. All patients were divided into two subgroups: with lone AF (n=94) and with concomitant arterial hypertension (n=80). All patients underwent a complex of clinical, instrumental (ECG, echocardiography, computed tomography of the pulmonary veins) and laboratory tests (thyroid hormones, inflammatory markers, fibrosis), as well as genetic analysis (determination of single nucleotide polymorphisms described as AF risk factors in genes AGXT2, PDE4D, SLN, SCN5A, PITX2, PRRX1, ZFHX3, TBX5, CAV1 и HCN4).
 Results: For the rare polymorphisms rs12291814 (SLN) and rs137854601 (SCN5A) wasnt found anyone carrier of the minor allele (C and A, respectively). In the both patient subgroups the minor allele T of rs2200733 in PITX2 (OR=3.18, p0.0001), minor allele G of rs3903239 in PRRX1, and minor alleles A of 2 polymorphisms rs2106261 and rs7193343 in ZFHX3 gene were revealed as risk factor of AF (OR=2.96, p0.0001, OR=2.02, p=0.0045, OR=1.64, p=0.04, respectively). We also revealed significant difference between AF and control groups for rs3807989 in CAV1: homozygotic state of minor allele A has a protective effect on the development of arrhythmias (OR=0.39).
 Conclusions: We revealed the association between the polymorphisms in genes regulating transcription and the development of atrial fibrillation. These polymorphisms have already described but their frequencies have never investigated in Russian population. But the polymorphisms influence to gene functions stays unclear, although attempts to investigate relationship between genotype and gene expression have been made. When the relationship will be discovered it can help us to modify our approach in treatment to patients with atrial fibrillation.

Gene Polymorphism of Xenobiotic Biotransformation Enzymes in Patients with Classical Ph-Negative Myeloproliferative Neoplasms.

The correlation of gene polymorphisms rs4025935 (large deletion), rs1695 (313A>G), rs71748309 (large deletion), and rs1800566 (609C>T) of GSTM1, GSTT1, and NQO1 genes encoding glutathione-S-transferases (GST) M1, P1, and T1 and NADPH-quinone oxidoreductase with the risk of development of classical Ph-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) was studied in the Caucasian ethnicity population of Vyatka region of the Russian Federation. It was found that NQO1*609T allele, NQO1*609T genotypes, and homozygous carriage of a deletion (null) allele of GSTT1 gene are associated with the risk of development of myeloproliferative neoplasms (OR=1.29, 95%CI=1.02-1.64, p=0.04; OR=1.39, 95%CI=1.04-1.85, p=0.03; and OR=1.48, 95%CI=1.03-2.12, p=0.03, respectively). However, no influence of GSTM1 and GSTP1 gene polymorphisms on the risk of development of myeloproliferative disorders was registered.

LPP and RYR2 Gene Polymorphisms Correlate with the Risk and the Prognosis of Astrocytoma.

Astrocytoma is the most common neuroepithelial tumor. Genetic factors play an important role in the development and prognosis of astrocytoma. So this study focuses on the impact of LPP and RYR2 genes on the occurrence and prognosis of astrocytoma. Rs12594 and rs16835904 in the RYR2 gene and rs1064607, rs3796283, and rs2378456 in the LPP gene were selected and genotyped using Agena MassARRAY in 365 patients and 379 healthy populations. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression to assess the influence of gene polymorphisms on occurrence of astrocytoma. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, the log-rank test, and the Cox regression analysis. The survival rates of patients receiving gross total resection and postoperative chemotherapy were higher than patients receiving near total resection and subtotal resection and without chemotherapy. In recessive model, the patients with LPP rs2378456 CC genotype increased the risk of astrocytoma (OR = 1.43, 95% CI 1.01-2.02, p = 0.042). Stratified analysis shows that RYR2 rs16835904 TC-TT genotype facilitated the risk of astrocytoma in male (OR = 1.93, 95% CI 1.15-3.24, p = 0.011). Cox regression analysis shows that RYR2 rs12594 AA genotype and AG genotype were associated with OS of astrocytoma (AG genotype: HR = 1.62, 95% CI 1.04-2.53, p = 0.034; AA genotype: HR = 1.70, 95% CI 1.08-2.68, p = 0.021). RYR2 and LPP genes were found to affect the occurrence and prognosis of astrocytoma.

Influence of dopaminergic system gene polymorphisms on mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays

BackgroundThe dopaminergic pathways have previously been reported to be involved in drug dependence. The candidate gene involved in the dopaminergic function has been associated with substance abuse.ObjectiveThe objective of the study is to investigate the possible association between dopaminergic system gene polymorphisms with mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays. The study has never been done anywhere else, due to its unique population of study subjects.Subjects and methodsIn this study, genetic polymorphisms of dopamine D2 receptor (DRD2) dopamine transporter (SLC6A3), dopamine beta-hydroxylase (DβH), and norepinephrine transporter (SLC6A2) in Malay males (n = 70) having mixed amphetamine-type stimulant (ATS) and opioid dependence were compared with those in control subjects (n = 87). DNA was extracted from leucocytes followed by single nucleotide polymorphism (SNP) determination using PCR-RFLP. The association of the gene with drug dependency was analyzed using chi-squared tests.ResultsThere was a significant difference between the genotype (χ2 = 10.048, p < 0.01) and allele frequency (χ2 = 14.039, p = 0.000) of the DRD2 rs1800497 gene in the drug dependence group as compared to the control. There was also a significant difference in DβH rs1611115 at the allelic (χ2 = 4.483, p = 0.034) but not at genotypic levels (χ2 = 7.572, p = 0.23) in both control and drug dependence groups. There was an association for SLC6A3 rs27072 with drug dependence at the genotypic level (χ2 = 7.006, p = 0.030) although no significant difference exist at the allelic level (χ2 = 2.091, p = 0.148). No significant difference was observed in SLC6A2 rs3785157 genes polymorphism at both genotype and allelic level in control and drug dependence group respectively (χ2 = 0.94, p = 0.954) (χ2 = 0.29, p = 0.865) indicating that these polymorphisms do not affect drug dependence.ConclusionOur study suggests that DRD2 rs1800497, DβH rs1611115, and SLC6A3 rs27072 but not SLC6A2 rs3785157 are associated with drug-dependent behavior among Malaysian Malays.

Effect of IL2RA and IL2RB gene polymorphisms on lung cancer risk

BackgroundInflammation is crucial for lung cancer development. Variants of multiple genes in inflammation pathways may lead to susceptibility to lung cancer. In the present study, we aimed to assess the influence of polymorphisms in inflammation-related genes (IL2RA and IL2RB) on lung cancer risk. MethodsA total of 507 patients with lung cancer and 503 healthy controls were genotyped for seven polymorphisms of IL2RA and IL2RB using the Agena MassARRAY platform. We evaluated the relationship of the genotypes with lung cancer susceptibility using odds ratio (OR), 95% confidence interval (95% CI) and chi square test. ResultsWe found that IL2RA rs12722498 was significantly associated with a decreased risk of lung cancer in dominant (p = 0.040, OR = 0.71, 95% CI = 0.51–0.98), additive (p = 0.016, OR = 0.68, 95% CI = 0.50–0.93) and allele (p = 0.019, OR = 0.69, 95% CI = 0.51–0.94) models. After stratification analysis, the results showed that IL2RA rs12569923 (non-smokers), IL2RA rs791588 (≤60 years old, non-drinkers, BMI < 24 kg/m2), IL2RA rs12722498 (≤60 years old, non-drinkers, BMI < 24 kg/m2, female) and IL2RB rs2281089 (female, stage) significantly decreased the risk of lung cancer. Additionally, the haplotypes of rs12569923 and rs791588 in IL2RA had strong relationships with lung cancer in the subgroups of BMI < 24 kg/m2, age ≤ 60 years old, non-smokers and non-drinkers. ConclusionOur results showed that the IL2RA and IL2RB polymorphisms were associated with lung cancer risk in the Chinese Han population, which suggests roles for IL2RA and IL2RB polymorphisms in lung cancer.

Functional Genetic Variant of Long Pentraxin 3 Gene Is Associated With Clinical Aspects of Oral Cancer in Male Patients.

Long pentraxin 3 (PTX3) is produced by various cell types and is correlated with tumor progression in various tumor types. However, the clinical significance of PTX3 polymorphisms in oral cancer and their correlation with the risk of cancer are still unclear. In this study, we assessed the influence of PTX3 gene polymorphisms and environmental factors on susceptibility to oral tumorigenesis. We recruited 865 cases with oral cancer and 1,189 controls. Four single-nucleotide variations of the PTX3 gene (rs1840680, rs2305619, rs3816527, and rs2120243) were verified using a real-time polymerase chain reaction in control participants and cases with oral cancer. We found that rs3816527 in smokers was correlated with the development of late-stage cancer (odds ratio [OR], 2.328; 95% confidence interval [CI], 1.078–5.027) and increased lymph node metastasis (OR, 2.152; 95% CI, 1.047–4.422). Moreover, additional bioinformatics analysis results showed that the rs3816527 C allele variant to the A allele exhibited the strongest exonic splicing enhancer activity. In conclusion, our results suggested that PTX3 rs3816527 plays a role in oral cancer development.

APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR.

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9-25.5, p < 0.001) increased risk of bleeding, and attributable risk was 88.3%. C allele carriers of c.1853C>T had 6.4 times (95% CI 2.3-17.9, p < 0.001) increased risk of bleeding after adjusting for covariates (attributable risk of 84.3%). AUROC values of models that included c.1853C>T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.

Influence of genetic polymorphisms in DICER and XPO5 genes on the risk of coronary artery disease and circulating levels of vascular miRNAs

IntroductionSingle-nucleotide polymorphisms (SNPs) in microRNA (miRNA) machinery genes may affect the regulatory capacity of miRNAs by impacting their biogenesis. The aim of the study was to analyze the association between SNPs in two key genes (DICER rs1057035T>C and XPO5 rs11077A>C) and coronary artery disease (CAD) risk as well as to examine their effects on circulating levels of vascular miRNAs. Materials and methodsWithin the Italian GENOCOR cohort, we studied a cohort of 557 patients (502 males, 57 ± 9 years) with angiographically documented CAD. A total of 443 healthy controls (262 males, 56 ± 12 years) was also enrolled. Genotyping was determined by using a TaqMan®SNP genotyping assay. Analysis of miR-132 and miR-140-3p was assessed in a subset of 70 CAD patients by using qRT-PCR. ResultsThere were statistically significant differences between CAD patients and healthy controls in the distribution of both DICER and XPO5 genotypes (p = 0.03 and p = 0.02, respectively). Multivariate analysis showed a significantly decreased risk of CAD by 50% in patients with DICER rs105703CC genotype as compared to TC heterozygote and TT homozygote patients (ORadjusted = 0.50; CI: 0.30–0.83, p = 0.007). In a recessive model, the XPO5 rs11077CC genotype was associated with a 32% reduced risk of CAD (ORadjusted = 0.68; CI: 0.30–0.99 p = 0.047). XPO5 rs11077CC genotype was significantly associated with higher levels of both miRNA-132 (p = 0.04) and miRNA-140-3p (p = 0.03). ConclusionsGenetic polymorphisms in DICER and XPO5 genes are associated with a decreased risk of CAD, probably by impacting expression levels of vascular and cardiac-specific miRNAs. Further studies are needed to better elucidate the biological relevance of both variants in CAD development.

The Role of Genetic Polymorphism in the Formation of Arterial Hypertension, Type 2 Diabetes and their Comorbidity.

Hereditary component plays a significant role in the formation of insulin resistance (IR) - one of the pathogenetic links of arterial hypertension (AH) and type 2 diabetes mellitus (DM2). However, the genetic predisposition to IR can not be realized and does not manifest itself clinically in the absence of appropriate factors of the environment (excessive nutrition, low physical activity, etc.). The review summarizes the results of studies which describe the contribution of genetic polymorphism to the formation and progression of AH, DM2 and their comorbidity in various populations. In many studies, it has been established that genetic polymorphism of candidate genes is influenced by the formation, course and complication of AH and DM2. According to research data, the modulating effect of polymorphism of some genetic markers of AH and DM2 on metabolism and hemodynamics has been established. The results of numerous studies have shown a higher frequency of occurrence of AH and DM2, as well as their more severe course with adverse genetic polymorphisms. At the same time, the role of genetic polymorphism in the formation of AH and DM2 differs in different populations. Contradictory data on the influence of gene polymorphisms on the formation of AH and DM2 in different populations, as well as a small number of studies on the combined effects of several polymorphisms on the formation of comorbidity, determine the continuation of research in this direction.

MMP20 Single-Nucleotide Polymorphisms Correlate with Susceptibility to Alcohol-Induced Osteonecrosis of the Femoral Head in Chinese Males.

BackgroundAlcohol-induced osteonecrosis of the femoral head (ONFH) is caused by the interaction of genetic and environmental factors. Genetic variations of matrix metalloproteinase (MMP) system are associated with ONFH development and progression. In this study, we aimed to evaluate the relationships between MMP20 gene polymorphisms and the risk of alcohol-induced ONFH in Chinese Han males.Material/MethodsIn this case-control study, genotypes of 14 selected SNPs in the MMP20 gene were assayed using MassARRAY in 299 male cases with alcohol-induced ONFH and in 197 healthy males. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of gene polymorphism on occurrence of alcohol-induced ONFH by allelic model analysis, genotype model analysis and haplotype analysis.ResultsAfter allelic model analysis, the minimum alleles of rs10895322, rs1784424, rs3781788, and rs1573954 correlated with an increased risk of alcohol-induced ONFH (P<0.05). Genetic model analysis revealed significant associations of 9 SNPs with alcohol-induced ONFH occurrence even after adjustment for age (P<0.05): 2 protective SNPs (rs1711423 and rs1784418) and 7 high-risk SNPs (rs10895322, rs1784424, rs3781788, rs7126560, rs1573954, rs1711399, and rs2292730). Moreover, 8 SNPs showed a statistically significant association with different clinical phenotypes (P<0.05). Beyond that, haplotype “CGGTTCCA” in MMP20 was discovered to correlate with a 1.63-fold increased risk of alcohol-induced ONFH (OR: 1.63, 95% CI: 1.15–2.30, P=0.0058).ConclusionsOur data sheds new light on the associations of MMP20 gene polymorphisms with alcohol-induced ONFH predisposition in Chinese Han males.

SAT-021 Efficacy of Vitamin D Supplementation According to Vitamin D Binding Protein Polymorphisms

The study aimed to determine the influence of DBP gene polymorphisms in vitamin D metabolites before and after vitamin D supplementation. Out of 234 participants (126 females and 108 males), 146 had vitamin D deficiency (25(OH)D <50nmol/l) and were given 2000IU daily dose of vitamin D for 12 months. Two common single nucleotide polymorphisms (SNPs), (rs4588 and rs7041) of the DBP gene were assessed. Post supplementation median 25(OH)D was significantly higher [61.2 (46.3-76.8) and 66.6 (53.2-83.7)] in participants with CC genotype of rs4588 and GG genotype of rs7041 than other genotypes (p<0.001). Participants with T allele are 2.9 (1.9-4.5) times more likely to be a non-responder (unable to achieve serum 25(OH)D post-supplementation) than those with G allele (p<0.001). Participants with A allele are 3.7 (2.1-6.6) times more likely to be a non-responder than those with C allele (p<0.001). Furthermore, participants with TT and TG are 6.2 and 4.2 times more likely to be a non-responder than those with the GG genotype (p-values <0.001) even after adjustments for age, gender, BMI, baseline 25(OH)D concentration and other alleles. Participants with AA and CA genotypes are 12.4 (1.4-110) and 4.1 (2.1-8.0) times more likely to be non-responders as compared to those with CC genotype but lost significance after adjustment. The SNPs, rs7041 and rs4588 variants of the DBP gene are associated with baseline 25(OH)D levels and modifies 25(OH)D response after vitamin D supplementation in Saudi adults.

The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.

BackgroundMalignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk.Patients and methodsIn total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms.ResultsERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41–0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12–11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19–0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk.ConclusionsOur findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.

The Influence of GPX1 Pro198Leu, CAT C262T and MnSOD Ala16Val Gene Polymorphisms on Susceptibility for Non-Hodgkin Lymphoma and Overall Survival Rate at Five Years from Diagnosis

Abstract Objective: The aim of the current study was to investigate possible associations between catalase C262T (CAT C262T), glutathione peroxidase 1 Pro198Leu (GPX1 Pro198Leu), manganese superoxide dismutase Ala16Val (MnSOD Ala16Val) gene polymorphisms and non-Hodgkin Lymphoma risk (NHL) in a Romanian population and the five-year overall survival rate of the NHL patients. Methods: We included in this case-control study 406 individuals, divided into two groups: the control group (n=315) and the patients group (n=91). The DNA was extracted from peripheral blood and amplified using specific techniques. Results: The variant homozygous genotype of GPX1 Pro198Leu represents a risk factor for NHL development and no associations regarding the risk for NHL were found for MnSOD Ala16Val and CAT C262T gene polymorphisms. Two of the studied polymorphisms were associated with the overall survival rate thus: negative association regarding MnSOD Ala16Val, associated with higher overall survival rate and a positive one regarding CAT C262T, associated with lower overall survival rate. Conclusions: According to our results, the mentioned polymorphisms may be considered as susceptible markers of the five-year overall survival rate for NHL patients. Future studies with a larger number of patients are needed to confirm our results.

Influence of interleukin-6 gene polymorphism on the efficacy of antiviral treatment in patients with chronic hepatitis C

Aim. The aim of the work was to determine the influence of interleukin-6 gene polymorphism on the effectiveness of antiviral therapy in patients with chronic hepatitis C. Materials and methods. A total of 83 patients with chronic hepatitis C (CHC). were included in the study. The efficacy of therapy with the peg-IFNα + SOF + RBV was analyzed depending on the polymorphism of interleukin-6 gene (rs1800795). Results. All CHC patients with the CC genotype (14 – 100 %) responded to antiviral therapy with the peg-IFNα + RBV + SOF, but only 85.5 % of the patients with CG/GG genotypes responded (59 of the 69). In CHC patients with CG/GG genotypes, who responded to the therapy by SVR 24 formation, the HCV-RNA negativization was slower, in contrast to patients with the CC genotype, who showed a persistent absence of the virus in the blood from the 4th week of treatment. All patients with the CC genotype of IL-6 gene polymorphism presented complete normalization of ALT activity at this time if SVR 24 had been achieved. In the vast majority of CHC patients with SVR 24 and the CG/GG genotype after the therapy cessation, ALT activity continued to decrease and normalized after 24 weeks of observation in 94.9 % (56 of the 59). However, 20.0 % of patients with the CG/GG genotype who did not respond with the formation of SVR 24, had elevated serum ALT activity at the time of SVR 24 evaluation. Kendall’s rank correlation was performed to determine the factors, which statistically significantly affect the results of peg-IFNα + RBV + SOF therapy. IL-6 gene polymorphism had an effect on the efficacy of therapy, both on the HCV-RNA negativization in the blood at the end of treatment (P = 0.04) and on the achievement of SVR 24 (P = 0.03). The lack of response as well as the lack of SVR 12 and SVR 24 formation at the time of therapy completion were associated with the IL-6 gene CG/GG polymorphism presence and a higher index of ALT activity at the beginning of treatment (τ = -0,18, P < 0.01). Conclusions . In CHC patients, the CC genotype of IL-6 gene (rs1800795) is a favorable prognostic factor for the formation of SVR24 in the treatment of peg-IFNα + RBV + SOF. Patients who did not respond to the treatment by SVR 24 formation had only the IL-6 gene CG/GG polymorphism. Even in HCV patients with CG/GG genotypes who responded to the treatment by SVR 24 formation, the negativization of HCV-RNA in the blood was slower, unlike the patients with CC genotype. The absence of response at the time of therapy completion, as well as the absence of SVR 12 and SVR 24, were associated with the presence of the IL-6 gene CG/GG polymorphism and a higher level of ALT activity at the beginning of therapy (τ = -0,18, P < 0.01).

Downregulation of ABCB1 gene in patients with total hip or knee arthroplasty influences pharmacokinetics of rivaroxaban: a population pharmacokinetic-pharmacodynamic study.

Rivaroxaban is a substrate for ABCB1 transporter and is commonly used in patients undergoing hip or knee replacement surgery for thromboprophylaxis. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model to investigate the influence of ABCB1 gene expression and polymorphism on rivaroxaban exposure and anticoagulation effects. Five blood samples per patient were collected during 5days after the surgery for the determination of rivaroxaban concentration in plasma and for determination of prothrombin time and partial thromboplastin time. Non-linear mixed effects model was used for a population PK-PD analysis and for testing covariate effects. A one-compartment PK model with first-order absorption adequately described the pharmacokinetic data. The typical oral clearance (CL/F) was 6.12L/h (relative standard error, 15.8%) and was associated with ABCB1 expression. Compared to base line before the surgery, a significant ABCB1 downregulation was observed 5days after the surgery (p < 0.001). Prothrombin time and partial thromboplastin time were both linearly associated to the logarithm of the rivaroxaban plasma concentration. We confirmed that variable rivaroxaban CL/F is associated with ABCB1 expression, which is in accordance with previous studies on P-glycoprotein involvement in rivaroxaban PK. Furthermore, we observed the downregulation of ABCB1 expression after the surgery. The cause remains unclear and further research is needed to explain the underlying mechanisms.

Prosthetic valve thrombosis - association of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 genes.

Prosthetic Valve Thrombosis (PVT), in spite of the advances in the valve design and the material used, remains a serious complication of mechanical cardiac valve replacement. The factors influencing the development of PVT are: thrombogenicity of the valve, hemodynamics of the transprosthetic blood flow and ineffective anticoagulation. Genetic polymorphism of the genes VKORC1 (-1639 G > A and 1173 C > T), CYP2C9 (∗2 & ∗3 alleles) and CYP4F2 (1347 G > A) are known to influence the anticoagulant dose-effect response. Since there has not been any earlier study on the direct influence of gene polymorphism on the development of PVT, we investigated into this association.Genotyping for the genes VKORC1, CYP2C9 and CYP4F2 was carried out by conventional PCR-RFLP method for 91 consecutive PVT patients. Subjects of our earlier study served as controls (n = 136).Female patients and patients with smaller prosthetic valve size were more prone to developing PVT (68%, n = 62). Patients bearing A allele of CYP4F2 1347 G > A polymorphism exhibited a fivefold increased risk of PVT (OR = 5.022 (1.39–18.04), P = .013). G allele of VKORC1 when analyzed in combination of genotypes showed a fourteen fold increased risk for developing PVT (OR = 14.25 (5.52–36.77), P = 0.001). CYP2C9 (∗2&∗3) gene polymorphism did not show any significant association with PVT (OR = 1.54 (0.128 – 18.82), P = .731).Patients bearing A allele of CYP4F2 showed an increased risk of developing PVT in our case – control study.

Transmembrane G protein-coupled receptor 30 gene polymorphisms and uterine adenomyosis in Korean women

To compare the genetic distributions of 14G protein-coupled receptor 30 (GPR30) single-nucleotide polymorphisms (SNPs) between women with and without uterine adenomyosis. The study population comprised 69 Korean women. Uterine tissues from the adenomyosis and non-adenomyosis groups were used for DNA extraction. Pre-designed PCR/Sanger or Sequencing Primer and TaqMan® SNP Genotyping Assays were used for the SNP genotyping of the GPR30 gene. Immunohistochemical staining was performed to confirm the GPR30 expression. Differences in genotype and allele frequencies between the two groups were calculated using Fisher’s exact test. The rs3802141 CT genotype was more common in the control group (p = .02), and the rs4266553 CC genotype was more common in the adenomyosis group (p = .02). The C allele of the SNP rs4266553 was more common in the adenomyosis group (p = .02). GPR30 expression was confirmed in 69 individuals in both groups. GPR30 gene polymorphism is presumed to affect the risk of adenomyosis with limited sample size. Further large-scale study is needed to explain the genetic influence of GPR30 gene polymorphism.

Corrigendum: Influence of IL28B and MxA gene polymorphisms on HCV clearance in Han Chinese population

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The influence of rs53576 and rs2254298 oxytocin receptor gene polymorphisms on plasma oxytocin levels and measures of empathy

Oxytocin achieves its effects after binding the oxytocin receptor (OXTR). Oxytocin plays an important role in empathy. The aim of this study was to examine the influence of two single nucleotide polymorphisms (SNPs) of the OXTR gene (rs53576 and rs2254298) on empathy measures and plasma oxytocin levels. Seventy-four university students were screened for the OXTR rs53576 and rs2254298 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The level of oxytocin in the plasma was measured by the enzyme linked immunosorbent assay (ELISA). All subjects were assessed with the empathy quotient (EQ) questionnaire and Reading the Mind in the Eyes Test (RMET). Subjects carrying the rs53576 GG genotype had a higher EQ score, compared to GA/AA genotype carriers. By gender analysis, significance was reached only in females. Considering the influence of both examined polymorphisms on empathy, participants with the GGGG diplotype had a higher EQ in comparison with GAGG/AAGG carriers. These hormone effects were not correlated with plasma oxytocin levels. This is the first study implying that higher empathy in rs53576 GG genotype carriers may not depend on plasma oxytocin levels, but possibly on the number and function of OXTRs in the brain.

Association of Apolipoprotein E Gene Polymorphism with Lipid Profile in Patients with Acute Coronary Syndrome in Han Chinese: A Critical Review

This review paper focuses on the genetic contribution, in particular, the association of Apolipoprotein E gene polymorphism to lipid abnormality and subsequent acute coronary syndrome in Han Chinese of China. Many researches have been published pertaining the influence of ApoE gene polymorphism on coronary artery disease, dyslipidemia and the response of statin in Han Chinese. Most of the studies in Han Chinese like other populations demonstrated that ApoE 4 allele genetically predisposes coronary artery disease, acute coronary syndrome, severity of occlusion of coronary artery and higher incidence of major adverse cardiovascular events (In Han Chinese, ApoE allele carriers demonstrated 85% increase in major adverse cardiovascular events (MACE) in six months follow up). In addition, ApoE4 allele carrier also showed both increased in LDL level and decrease response to statin therapy in dyslipidemic Han Chinese. On the other hand, ApoE2 carrier is scavenger of cholesterol and triglyceride from the blood; thus it is cardiovascular-protective. Despite positive relationship between ApoE gene polymorphism and cardiovascular pathologies, prognostic outcome and resistance to intervention, this area of research still requires extensive investigation in Han Chinese. Because, several other studies revealed either negative effect or showed no effect by ApoE gene polymorphism on cardiovascular disease. Some of the causes of such debatable results could be explained by factors such as diminutive frequency allele and expression of ApoE gene in coronary heart disease. This part of the research yet requires extensive study with bulkier sample size and retrospective in nature, in order to ascertain the influence of ApoE genotype on lipid, anti-hyperlipidemic agent and coronary heart disease. Such studies could assist us to confirm whether to test healthier subjects to predict genetic risk of coronary heart disease in Han Chinese population. The aim of this review paper is to critically analyze the effect of ApoE gene on the occurrence of coronary heart disease in Han Chinese.