Rs1799983 Polymorphism Research Articles

Increased prevalence of the CVD-associated ANRIL allele in the Roma/Gypsy population in comparison with the majority Czech population.

Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P < 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.

Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity.

BackgroundThe main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.MethodsThis study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.ResultsThis study assessed 10 polymorphisms (rs11206510 within the PCSK9 gene, rs6725887 and rs7582720 within the WDR12 gene, rs4977574, rs10757278, and rs1333049 within the CDKN2A gene, rs2862116, rs7906426, rs1746048, and rs268322 within the CXCL12 gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).ConclusionCarriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).

Paraoxonase-1 (PON1) Status Analysis Using Non-Organophosphate Substrates.

Human paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme with antioxidant, anti-inflammatory, and antiapoptotic roles. The ability of PON1 to hydrolyze specific organophosphate (OP) compounds and prevent accumulation of oxidized lipids in lipoproteins has prompted a large number of studies investigating PON1's role in modulating toxicity and disease. Most of these studies, however, have only focused on PON1 single nucleotide polymorphism analyses and have ignored PON1 activity levels, arguably the most important parameter in determining protection against exposure and disease. We developed a two-substrate activity assay termed "PON1 status" that reveals both the functional PON1192 genotype and plasma PON1 activity levels. While our previous studies with PON1 status demonstrated that both PON1192 functional genotype and enzymatic activity levels obtained exclusively by determining PON1 status are required for a proper evaluation of PON1's role in modulating OP exposures and risk of disease, the original PON1 status assay requires the use of highly toxic OP metabolites. As many laboratories are not prepared to handle such toxic compounds and the associated waste generated, determination of PON1 status has been limited to rather few studies. Here, we describe a PON1 status protocol that uses non-OP substrates with a resolution equivalent to that of the original PON1 status approach. We have also included useful suggestions to ensure the assays can easily be carried out in any laboratory. The protocols described here will enable a proper examination of the risk of exposure or susceptibility to disease in PON1 epidemiological studies without the need to handle highly toxic substrates. © 2021 Wiley Periodicals LLC. Basic Protocol: Determining PON1 status using non-organophosphate substrates Support Protocol 1: Experimental pathlength determination Support Protocol 2: PON1 DNA genotyping for the Q192R (rs662) polymorphism.

NOS3 rs1799983 and rs2070744 polymorphisms and their association with advanced chronic kidney disease and coronary heart disease in Canarian population with type 2 diabetes.

Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Cross-sectional case-control study. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/min/1.73m2 and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes. A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

ASSOCIATION OF RS2200733 POLYMORPHISM WITH ANTIARRHYTHMIC THERAPY AND PROGRESSION OF ATRIAL FIBRILLATION IN THE UZBEK POPULATIO

Aim: to study the association of rs2200733 polymorphism with antiarrhythmic efficacy of amiodarone, propafenone and allapinin in the prevention of atrial fibrillation (AF) progression. Material and methods. In order to comparatively evaluate the effectiveness of antiarrhythmic drugs in the prevention of AF progression the analysis included 163 patients (54 (33.1%) – with persistent AF and 109 (66,9%) with paroxysmal) in age from 31 to 77 years (average age 52.16±12.64 years) with an initially restored sinus rhythm (pharmacological or electric cardioversion). To prevent relapse of AF one of the antiarrhythmic drugs (amiodarone, propafenone or allapinin) was recommended to patients. In order to identify the association of rs2200733 polymorphism in ATFB5 gene with AF the study included 69 patients who were initially diagnosed with paroxysmal (n=20) and persistent AF (n=49). The control group (n=30) consisted of individuals of Uzbek nationality without AF in age from 30 years to 77 years. Genotyping of samples for the allelic carriage of rs2200733 polymorphism was performed by PCR-RFLP. The results are presented as M ± SD. Results. It was shown that a persistent form of AF is prognostically unfavorable for AF progression. Moreover, in patients with AF progression the initial body mass index was significantly higher and a higher risk of developing heart failure was observed in the dynamics. The results indicate the predominance of the CC genotype and C allele of rs2200733 polymorphism in Uzbek patients with AF. A similar analysis performed in the control group (without AF) also showed a significant prevalence of the C allele and CC genotype. The association of TT genotype with a risk of AF was shown, since AF was more common among TT genotype carriers compared with CT and CC genotypes carriers (90% versus 67%, p<0.001). The limiting effect of TT carriage on the antiarrhythmic efficacy of the reference drug, amiodarone, in patients with AF was also noted. Conclusion. Thus, our study showed that the TT genotype of rs2200733 polymorphism is a genetic marker of the AF risk in Uzbek population. Carriers of TT genotype of rs2200733 polymorphism also have the most unfavorable prognosis for AF progression. Genotyping of the rs2200733 polymorphism in Uzbek patients with AF will allow differentially prescribing antiarrhythmic drugs and timely conduct procedure for radical elimination of arrhythmogenic substrate using radiofrequency ablation.

Evaluation of ICAM-1 rs5498 and rs3093030 Polymorphisms in Chinese Patients with Colorectal Cancer.

Colorectal cancer (CRC) is a common cancer threatening human health. Intercellular adhesion molecule-1 (ICAM-1, CD54) displays a key role in carcinogenesis and previous studies have suggested that ICAM-1 single-nucleotide polymorphisms (SNPs) are predicted to increase the risk of CRC. However, the relationship of ICAM-1 SNPs with CRC susceptibility was controversial. We conducted a case-control study to clarify the association of ICAM-1 SNPs (rs5498 and rs3093030) with the CRC risk. A total of 1003 CRC patients and 1303 controls were recruited to determine ICAM-1 SNPs (rs5498 and rs3093030) by SNPscan method. In the case-control study, we found that ICAM-1 rs5498 polymorphism did not influence CRC risk (AG vs. AA: adjusted p = 0.179; GG vs. AA: adjusted p = 0.281, AG+GG vs. AA: adjusted p = 0.398; GG vs. AA+AG: adjusted p = 0.153), and ICAM-1 rs3093030 polymorphism did not influence CRC risk (CT vs. CC: adjusted p = 0.841; TT vs. CC: adjusted p = 0.175, CT+TT vs. CC: adjusted p = 0.574 and TT vs. CC+TT: adjusted p = 0.180). In a subgroup of age >61, ICAM-1 rs5498 decreased the risk of CRC (p = 0.047). Multivariate analysis revealed that smoking (p = 0.002; odds ratio [OR]: 1.76, 95% confidence interval [CI]: 1.18-2.63), alcohol intake (p < 0.001; OR: 1.99, 95% CI: 1.31-3.05), and body mass index <24 (p < 0.001; OR: 1.55, 95% CI: 1.06-2.26) increased the risk of CRC. Our findings showed that ICAM-1 rs3093030 was not correlated with the susceptibility of CRC, and ICAM-1 rs5498 increased the risk of CRC in the subgroup of age ≥61. In the future, larger and ethnically homogeneous populations are needed to confirm our results.

Vascular endothelial growth factor (VEGF-2578 C > A) gene polymorphism as a genetic biomarker for breast cancer: A case control study

Breast cancer (BC) is one of the most frequently diagnosed cancers among Saudi women. Vascular endothelial growth factor (VEGF) is a key mediator of breast cancer angiogenesis. Hence, the present study was aimed to investigate the genetic association of VEGF (-2578 C > A, rs699947) polymorphism with BC among Saudi women. The present study includes 104 BC cases and 100 controls. Polymorphic analysis was carried out adopting polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) method. The homozygous variant (AA) (RR = 3.96, EF = 0.583, p = 0.005) and allele A (RR = 1.56, EF = 0.206, p = 0.03) of VEGF (-2578C > A) gene were significantly (p < 0.05) higher in the BC cases when compared to the controls. The recessive genotypes' combination (CC + CA) has shown a strong association (p = 0.003) with BC. Further, AA genotype has shown a strong association (p = 0.009) with BC in patients >40 years of age. AA genotype was significantly (p = 0.023) associated with advanced (T4) stage and high histologic tumor grades II (p = 0.015) and III (p = 0.006) of BC patients as well. Therefore, the homozygous variant and allele A of VEGF (−2578 C > A) gene polymorphism could be an associative genetic risk factor for BC in Saudi population. Regulatory region polymorphism in VEGF may help better to predict the risk of the BC at an early stage and will be assistive in the development of new diagnostic markers and treatment strategies.

THE NEW GENETIC ASPECTS OF ATRIAL FIBRILLATION IN PERSONS OF THE RUSSIAN POPULATION

Atrial fibrillation (AF) is one of the most common and dangerous heart rhythm disorders. Lone AF is due to a genetic predisposition. Foreign studies have proven the association of rs2200733 polymorphism of chromosome 4q25 with AF. No such studies have been conducted in the Russian Federation. Purpose of the study: to determine the association of the rs2200733 polymorphism of chromosome 4q25 with the development of AF, and to exclude the possible connection of the studied polymorphic marker with concomitant cardiovascular pathology. A total of 247 patients with AF were examined (113 from lone AF, 134 from secondary). Control group - 182 healthy people. Behavior: ECG, EchoCG, Holter ECG monitoring, blood test for thyroid hormones, VEM, CAG, molecular genetic research. In the group of patients with AF, the TT genotype was detected in 12.95%, which is statistically significant more often than in the control group (4.94%), p&lt;0.05. In the presence of a genotype with a rare T allele, the risk of developing AF increases by 1.5 times. The TT genotype was statistically significant more often in the subgroup of patients with isolated AF (17.70%) in comparison with the control group (4.94%), p&lt;0.05. The risk of developing isolated AF in the presence of a genotype with a rare allele T is 1.8 times increased. Chronic heart failure, no statistically significant differences were found (p&gt;0.05). In patients with the TT genotype, the mean LA size was 3.738 ± 0.494 cm, it was statistically significantly smaller than in patients with the CC genotype, which corresponded to 3.925 ± 0.629 cm, p&lt;0.05; and than in individuals with a heterozygous CT genotype, its value in this subgroup is 4.018 ± 0.639 cm, p&lt;0.05. Conclusions: Homozygous genotype for the rare TT allele and the T allele of the rs2200733 polymorphism of chromosome 4q25 are predictors of lone AF. The rs2200733 polymorphism has no association with any cardiovascular pathology, such as hypertension, ischemic heart disease and chronic heart failure. The TT genotype and the T allele of the rs2200733 polymorphism do not affect left atrial remodeling in patients with AF.

Relationship between rs3918242 Polymorphism of Matrix Methaloproteinase-9 Gene and Preeclampsia in Pregnant Women

Background: Preeclampsia is a complex disorder of pregnancy with an unknown etiology. Numerous studies have shown the possible role of gene polymorphisms, especially metalloproteinases, in development of this disease, but there are no definitive results. Objective: This study aims to investigate the possible association between rs3918242 (−1562C&gt;T) polymorphism in Matrix Metalloproteinase 9 (MMP9) gene with the risk of preeclampsia in pregnant women. Methods: In this cross-sectional study, participants were 90 pregnant women with preeclampsia and 199 healthy pregnant women (controls). The genotypes of rs3918242 polymorphism were investigated using Polymerase Chain Reaction technique and Limited Fragment Length Polymorphism method. Logistic regression analysis was used to investigate the relationship between rs3918242 polymorphism and preeclampsia. Findings: The frequency of CC, CT, TT genotypes of rs3918242 polymorphism was reported 47.8%, 47.8% and 4.2% in patients and 84.8, 13.1 and 2% in controls, respectively, and the difference between groups was significant (P&lt;0.001). The frequency of TT genotype in patients was significantly higher than in controls (P&lt;0.001). Moreover, the frequency of T allele in patients was 52.2%, while in controls it was 15.2% and the difference between the two groups was significant (P&lt;0.001). Conclusion: The rs3918242 polymorphism of MMP9 gene plays an important role in the incidence of preeclampsia in pregnant women.

THE rs2200733 POLYMORPHISM ON CHROMOSOME 4q25 AFFECTS THE EFFICIENCY OF PULMONALY VEIN ISOLATION IN PATIENTS IN ATRIAL FIBRILLATION

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, accounting for 1-2% in the general population. Currently, such a method of surgical treatment of AF as catheter ablation of the orifices of the pulmonary veins (CA PVV) is widely used. In the foreign literature in recent years, the results of single studies have appeared, which showed a clear association between the rs2200733 polymorphism and the occurrence of AF relapses after CA PVV. Such studies have not been conducted on the Russian population. Purpose of the study: to determine the relationship between the rs2200733 polymorphism of chromosome 4q25 and the efficiency of CA PVV in AF. A total of 113 patients with primary AF and 134 with secondary AF were examined. Control - 182 healthy people. A subgroup of 67 people was formed, with the conducted CA PVV from patients with primary AF. Conducted: ECG, EchoCG, Holter ECG monitoring, VEM, CAG, molecular genetic research. Among patients with recurrent AF after CA PVV, the TT genotype was detected statistically significantly more often than in patients without recurrence (20.00% relative to 0.00%, p&lt;0.05), while if there is a genotype with the T allele, the risk of AF recurrence increased 3.6 times (OR 3.636; CI 95% 1.324-9.991). The median relapse-free survival (which represents the time during which AF relapse occurs in 50% of patients) is 12.00 ± 0.66 months in the presence of the CT genotype (95% CI 10.70-13.30), 11.00 ± 2.99 months in patients with the TT genotype (95% CI 5.14-16.86). The median relapse-free survival was not determined in patients with the CС genotype, since the number of patients without signs of relapse of the disease was more than 50% by the end of the observation period. In this study, for the first time in the Russian population, it has been shown that the TT genotype and the T allele of the rs2200733 polymorphism are predictors of early recurrence of AF after CA PVV.

Genetic factors and the presence of coronary collaterals in patients with stable coronary artery disease

Abstract Background The coronary collateral circulation (CCC) varies in patients with coronary artery disease (CAD). Although many studies were provided to detect factors associated with collateral development, genetic factors are still studied insufficiently. The goal of this study was to assess the association of single nucleotide polymorphisms (SNP) in genes involved in vascular growth with CCC in patients with stable CAD. Purpose To assess if genetic variations in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (gene PLAU) are associated with the presence of coronary collaterals in patients with stable CAD. Methods A single-centered study was performed between March 2012 and December 2017. In 579 patients with stable CAD who underwent coronary angiography and had at least 50% stenosis in at least one major coronary artery collaterals were assessed by the use of the Rentrop score (0–3) during coronary angiography. SNPs PLAU rs4065, VEGF rs1570360, rs2010963 and rs699947, HGF rs5745752 were genotyped, multivariate logistic regression was carried out to determine the association of genotypes with CCC. Results 337 patients had visible coronary collaterals (Rentrop grade 1, 2 and 3) and 236 patients didn't have visible collaterals (Rentrop grade 0). Beside traditional risk factors of poor CCC - diabetes, smoking and arterial hypertension – patients without visible coronary collaterals (Rentrop 0) showed a higher frequency of the HGF rs5745752 CC genotype than those with visible coronary collaterals (Rentrop 1–3; p=0.001). (Fig. 1) The odds ratio of having CCC Rentrop 0 in patients with genotype CC was statistically significant (odds ratio = 1.94 [95% confidence interval: 1.38–2.76]; p=0.001). Statistical analysis showed that the PLAU rs4065 and VEGF rs1570360, rs2010963 and rs699947 polymorphisms were not associated with CCC (p&amp;lt;0.05). Conclusion An association was found between the HGF rs5745752 polymorphism and the CCC in patients with stable CAD. Patients with the CC genotype are at greater risk of developing poor coronary collaterals. Figure 1 Funding Acknowledgement Type of funding source: None

PON1 Q192R Gene Polymorphism and Pesticide Exposure Status of Rice Farmers, Suphan Buri, Thailand

PON1 Q192R (rs662) polymorphism in coding region is conveying differential catalytic activity oforganophosphate. Study was aimed to investigate PON1 Q192R gene polymorphisms in rice farmers alongwith pesticide knowledge and practices; and to evaluate the relationship of gene polymorphisms and serumcholinesterase (SChE) levels. Information of pesticide exposure, knowledge and practices were collectedfrom 50 rice farmers and 50 control respondents by questionnaire interviewing. Each blood sample wasobtained by venipuncture and prepared to serum for SChE activity test by paper test and automatic analyzer;to EDTA blood for genotyping by PCR-RFLP. Exposure status, knowledge and practices on pesticide usewere represented as frequency. Chi-square was used to analyze on the different of personal information;and of polymorphism. Independent t-test was used for comparison of SChE levels. Person correlation wasevaluated relationship between SChE level and genotypes. 60% of rice farmers were used pesticide over10 years. Rice farmers were long-term pesticide exposure with good on pesticide knowledge, howeverpoorly practice. Means of SChE level of both groups were within reference value and significantly different(p = 0.033). Polymorphisms were included wild type (QQ), heterozygote (QR) and homozygote (RR);and were significantly different between rice farmers (high frequency of RR genotype) and control (p =0.02). Relationship of polymorphism and SChE level were negative correlated (r = -0.261; p = 0.031). Thispolymorphism may useful biomarker for chronic pesticide exposure in Thai rice farmer and corresponded todecline of serum cholinesterase; and RR genotype was high risk group.

Genotyping of 2 Cholesteryl Ester Transfer Protein Gene Variants Among Coronary Artery Disease Patients

Introduction: Coronary artery diseases (CAD) are still among the top causes of death in most populations. The polymorphisms of the cholesteryl ester transfer protein (CETP) gene can influence the risk of CAD through modulating cholesterol metabolism. In this regard, the current study aimed to determine the role of the 2 important CETP gene polymorphisms in CAD patients. Methods: To this end, DNA was extracted from the whole blood of 100 CAD patients and 100 healthy controls and then subjected to polymerase chain reaction-restriction fragment length polymorphism for the genotyping of rs5882 and rs708272 polymorphisms.Results: Based on the results, no meaningful association was found between rs5882 and rs708272 polymorphisms, neither separately nor in combination, and the risk of CAD. However, the risk of CAD significantly increased in male rs5882 polymorphism carriers (P = 0.01). Finally, no significant association was demonstrated between serum high-density lipoprotein levels and the genotypes or alleles of neither rs5882 nor rs708272 polymorphism. Conclusion: Despite the finding regarding the lack of an association between CAD and the studied polymorphisms of the CETP gene, the importance of those variants in CETP protein function and CAD pathogenesis warrants further investigation on larger populations.

Association of PICALM with Cognitive Impairment in Parkinson's Disease.

Cognitive impairment is one of the most disabling nonmotor symptoms in Parkinson's disease (PD). Recently, a genome-wide association study in Alzheimer's disease has identified the PICALM rs3851179 polymorphism as one of the most significant susceptibility genes for Alzheimer's disease after APOE. The aim of this study was to determine the potential role of PICALM and its genetic interaction with APOE in the development of cognitive decline in PD. A discovery cohort of 712 patients with PD were genotyped for PICALM (rs3851179) and APOE (rs429358 and rs7412) polymorphisms. The association of PICALM and APOE-PICALM genetic interaction with cognitive dysfunction in PD was studied using logistic regression models, and the relationship of PICALM with cognitive decline onset was assessed with Cox regression analysis. PICALM effect was then replicated in an international, independent cohort (Parkinson's Progression Markers Initiative, N = 231). PICALM rs3851179 TT genotype was significantly associated with a decreased risk of cognitive impairment in PD (TT vs. CC + CT, P = 0.041, odds ratio = 0.309). Replication studies further demonstrated its protective effect on cognitive impairment in PD. In addition, the protective effect of the PICALM rs3851179 TT genotype was more pronounced in the APOE ε4 (-) carriers from the discovery cohort (P = 0.037, odds ratio = 0.241), although these results were not replicated in the Parkinson's Progression Markers Initiative cohort. Our results support the fact that PICALM is associated with cognitive impairment in PD. The understanding of its contribution to cognitive decline in PD could provide new targets for the development of novel therapies. © 2020 International Parkinson and Movement Disorder Society.

Impact of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinase 2 Gene Polymorphisms on Allograft Rejection in Pediatric Renal Transplant Recipients.

Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients. Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested. Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P < .05). Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.

Rs10490924 surrounding HTRA1/ARMS2 regulates the susceptibility of age-related macular degeneration

Multiple studies have assessed the contribution of rs10490924 on chromosome 10q26 surrounding HTRA1/ARMS2 gene to age-related macular degeneration (AMD) risk. However, the causal allele at this locus is still inconclusive. In this meta-analysis, we systematically characterized the potential association between rs10490924 polymorphism and AMD risk. Data available from 12 case-control studies, including a total of 5244 cases and 2755 controls in three different ethnic populations, were used to evaluate the correlation between rs10490924 G/T polymorphism (Ala69Ser) and AMD risk. In overall populations, the results indicated the Ala69Ser polymorphism was significantly associated with AMD under allelic (OR = 0.35, 95% CI = 0.30–0.40), homozygous (OR = 0.12, 95%CI = 0.09–0.17), dominant (OR = 0.18, 95%CI = 0.14–0.24), recessive (OR = 0.33, 95%CI = 0.28–0.39), and heterozygous genetic models (OR = 0.26, 95% CI = 0.21–0.33). Similar results were observed in subgroup analysis. This meta-analysis suggests that rs10490924 (Ala69Ser) polymorphism was significantly associated with the susceptibility of AMD in all ethnicities, Ala69 carriers are resistant to AMD risk.

The APOA5-rs662799 Polymorphism Is a Determinant of Dyslipidemia in Vietnamese Primary School Children.

Apolipoprotein A-V encoded by apolipoprotein 5 (APOA5) gene plays an important role in lipid metabolism, especially in the regulation of plasma triglycerol levels. The study aimed to evaluate the association of the APOA5-rs662799 polymorphism with dyslipidemia in Vietnamese children and the potential modification of obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) on this association. A case-control study was conducted with a total of 154 dyslipidemia cases and 389 controls at the age of 6 to 10 recruited at 31 primary schools in Hanoi city of Vietnam. Genotype for APOA5-rs662799 polymorphism was determined by the restriction fragment length polymorphism analysis. The association of APOA5-rs662799 polymorphism with dyslipidemia adjusting for age, sex, residence, and obesity-related traits was analyzed by binary logistic regression analysis. The results showed that in comparison with T/T and T/C carriers, the C/C carriers had a higher concentration of serum TAG in cases (p =0.049). Carriers of the C allele (C/C + T/C) had higher risk for developing dyslipidemia and hypertriglyceridemia than subjects with T/T genotype (odds ratio, OR = 1.7, p =0.0062 and OR = 1.6, p = 0.026, respectively). The association remained significant after adjusting for age, gender, residence, and obesity status (OR = 1.75, p = 0.006 and OR = 1.53, p = 0.049, respectively) or other obesity-related traits. The study suggested that the APOA5-rs662799 polymorphism may be a determinant of dyslipidemia and hypertriglyceridemia in Vietnamese children, independent of obesity-related traits.

Associations Between Common Polymorphisms of CDKN2B-AS and Susceptibility to ASCVD.

This meta-analysis was conducted to estimate associations between CDKN2B antisense (CDKN2B-AS) polymorphisms and susceptibility to atherosclerotic cardio-cerebral vascular diseases (ASCVD). A systematic literature research of PubMed, Medline, Web of Science, Embase, and CNKI was performed to identify eligible studies. Overall, 34 studies were included for meta-analyses. Pooled overall analyses showed that rs1333040, rs1333049, rs2383206, and rs2383207 polymorphisms were associated with susceptibility to ASCVD in the whole population. Further analyses by ethnicity revealed that all investigated polymorphisms were associated with susceptibility to ASCVD in East Asians. Moreover, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms were associated with susceptibility to ASCVD in West Asians, while rs2383206, rs10757274, and rs10757278 were associated with susceptibility to ASCVD in Caucasians. When we stratified eligible studies by type of disease, positive results were found for all investigated polymorphisms in patients with coronary artery disease (CAD) or myocardial infarction, whereas positive results were only detected for rs2383206 and rs10757274 polymorphisms in patients with ischemic stroke (IS). Our findings suggest that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms might serve as genetic biomarkers of CAD, and rs2383206 and rs10757274 polymorphisms might serve as genetic biomarkers of IS.

Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism.

The aims of the present study were to investigate the clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma (EOC) who have progressed after standard regimens, and to analyze the vascular endothelial growth factor receptor 2 (VEGFR2) rs2071559 polymorphism. A total of 118 patients with advanced EOC who received apatinib treatment were included in the study. Tumor response was evaluated using progression-free survival (PFS) and overall survival (OS) time, and safety data were documented. Additionally, peripheral blood and peripheral blood mononuclear cell (PBMC) specimens from the patients with EOC were collected to perform the genotyping of genetic polymorphism and assess the mRNA expression of VEGFR2, respectively. The objective response rate across the 118 patients with advanced EOC was 38.98%, the disease control rate was 63.56%, the median PFS time was 4.65 months and the median OS time was 15.10 months. Regarding the polymorphism analysis, the prevalence of rs2071559 in VEGFR2 among the 118 patients with advanced EOC was recorded as the TT genotype in 72 cases (61.02%), TC genotype in 41 cases (34.75%) and CC genotype in 5 cases (4.23%), and the minor allele frequency of rs2071559 was 0.22. The distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.781). TC and CC genotypes were merged in the subsequent analysis. The prognosis analyses suggested that the median PFS time of patients with the TC/CC genotype and the TT genotype was 3.10 and 5.40 months, respectively (P=0.015). Moreover, the median OS time of the two genotypes was 12.60 and 17.50 months, respectively (P=0.009). However, no association was noted between genotype status of the polymorphism and adverse reactions. Additionally, the mRNA expression analysis indicated that the mRNA expression levels of VEGFR2 in PBMC specimens were significantly different between TT and TC/CC genotypes (P<0.001). The present study suggested that the clinical outcomes of patients with advanced EOC, who progressed after standard regimens and received apatinib treatment, might be influenced by the VEGFR2 rs2071559 polymorphism.

The Influence of Endothelial Nitric Oxide Synthase (eNOS) Genetic Polymorphisms on Cholesterol Blood Levels Among Type 2 Diabetic Patients on Atorvastatin Therapy.

Endothelial nitric oxide synthase (eNOS) plays a major role in the response of anti-hypercholesterol statin drugs. Genetic polymorphisms in the eNOS gene affect the activity of eNOS thereby modulating the statin response. This study investigated the influence of major functional eNOS gene polymorphisms (rs2070744, rs1799983, and rs61722009) on the lipid profile of type 2 diabetes mellitus (T2DM) Jordanian patients treated with atorvastatin. The sample comprised 103 T2DM patients who attended the diabetes clinic of Jordan University Hospital. The T2DM patients had regularly been taking 20 mg atorvastatin. The atorvastatin response was calculated by measuring the lipid profile before and after three months of atorvastatin treatment. The eNOS genotypes of the subjects were analyzed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) assay. No significant association was found between eNOS genetic polymorphisms and the response to atorvastatin (ANOVA, p > 0.05). In addition, no significant difference in the frequency of eNOS genotypes was found between T2DM patients and healthy subjects. However, patients with eNOS rs1799983, 4a/4a, and rs61722009 G/G genotypes showed significantly lower levels of baseline total cholesterol (TC) and low density lipoprotein (LDL) than did patients carrying the rs1799983 4b/4b or rs61722009 T/T genotype (p < 0.05). The eNOS rs1799983 and rs61722009 polymorphisms were in complete linkage disequilibrium (D' = 1). Although no association was found between eNOS genetic polymorphisms and atorvastatin response, there was a significant association between the rs1799983 and rs61722009 genotypes and baselines levels of TC and LDL in Jordanian T2DM patients. These genetic variants affect cholesterol levels and may play a role in the susceptibility to cardiovascular diseases in T2DM patients. Further studies are needed to validate these findings.