scholarly journals Association between SCN1A polymorphism rs3812718 and valproic acid resistance in epilepsy children: a case–control study and meta-analysis

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Zhi Jian Wang ◽  
Jie Chen ◽  
Hai Liang Chen ◽  
Lin Yan Zhang ◽  
Duo Xu ◽  
...  

Resistance to valproic acid (VPA), a first-line antiepileptic drug (AED), is occurring at an alarming rate, particularly in children. Signal nucleotide polymorphisms are considered crucial in this process. Therefore, we investigated whether the SCN1A polymorphism rs3812718 could be associated with VPA resistance. A total of 231 children with epilepsy who were solely administered VPA were enrolled. DNA was extracted from the peripheral blood samples and was genotyped by the Mass Array method. Furthermore, a meta-analysis was conducted between the drug responsive and resistant patients who were exposed to voltage-gated sodium channels. Results revealed that the TT genotype was associated with a higher risk of developing drug resistance (OR = 2.636, 95% CI 1.08–6.433, P = 0.033). After adjusting for the risk factors, a significant difference was still observed between the responsive and resistant groups (OR = 2.861, 95% CI 1.141–7.174, P = 0.025). Moreover, the recessive model was associated with a decreased drug resistance (OR = 0.402, 95% CI 0.167–0.968, P = 0.042) after correcting the risk factors. Meta-analysis of nine studies revealed similar results. In conclusion, our results proved that the rs3812718 TT genotype was associated with a high risk of developing drug resistance, and the recessive model could decrease the risk of VPA resistance.

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yan-Hong Li ◽  
Jun-Yi Luo ◽  
Bin-Bin Fang ◽  
Guo-Li Du ◽  
Ting Tian ◽  
...  

Abstract Background CCN1 plays a crucial role in the modulation of cardiovascular diseases. However, whether CCN1 genetic variants are involved in the susceptibility of ACS remains unknown. Hence, the present study investigates the association between CCN1 polymorphisms and ACS among Han and Uygur populations in Xinjiang, China. Results In this case-control study, 1234 Han (547 ACS patients and 687 controls) and 932 Uygur (471 ACS patients and 461 controls) were genotyped using SNPscanTM for three single-nucleotide polymorphisms (SNPs, rs6576776, rs954353, and rs3753794) of the human CCN1 gene. In the Uygur population, we found that the detected frequencies of the C allele (25.3% vs. 18.3%, P<0.001) and CC genotype (6.4% vs. 3.0%, P=0.001) of rs6576776 were significantly higher in the ACS patients than in the control participants. Differences in rs6576776 regarding the dominant model (CC+CG vs. GG, 44.2% vs. 55.8%, P=0.001) and the recessive model (CC vs. CG+GG, 6.4% vs. 93.6%, P=0.016) were observed between the two groups. The frequencies of the GGC and AGC haplotypes in those with ACS were significantly higher than those in the control group (all P<0.05) in the Uygur population. After adjusting for hypertension, diabetes, lipids and smoking, all of which indicate that the rs6576776 C allele is associated with higher risk of ACS (odds ratio (OR)=1.798, 95% confidence interval (CI), 1.218-2.656, P=0.003). In Han population, neither the distribution of genotypes and alleles of the CCN1 gene three SNPs nor the distribution of haplotypes constructed with the three SNPs exhibited a significant difference between the ACS patients and control participants. Conclusions Our study document that the CCN1 gene rs6576776 C allele is associated with higher susceptibility of ACS and that the frequencies of GGC and AGC haplotypes are higher among the Uygur ACS patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Durray Shahwar A. Khan ◽  
La-Raib Hamid ◽  
Anna Ali ◽  
Rehana A. Salam ◽  
Nadeem Zuberi ◽  
...  

Abstract Background There is dearth of information on COVID-19’s impact on pregnant women. However, literature reported trends of COVID-19 differ, depending on the presence of clinical features upon presentation. Objective This systematic review aimed to assess differences in risk factors, management, complications, and pregnancy and perinatal outcomes in symptomatic vs. asymptomatic pregnant women with confirmed SARS-CoV-2 infection. Methods A search was run on electronic databases to identify studies reporting COVID-19 in pregnancy. Meta-analysis was performed and odds ratios and mean difference with 95% confidence intervals were calculated using Review Manager 5.4. Review Prospero registration number CRD42020204662. Results We included ten articles reporting data from 3158 pregnancies; with 1900 symptomatic and 1258 asymptomatic pregnant women. There was no significant difference in the mean age, gestational age, and body mass index between the two groups. The meta-analysis suggested that pregnant women who were obese (OR:1.37;95%CI:1.15 to 1.62), hypertensive (OR:2.07;95%CI:1.38 to 3.10) or had a respiratory disorder (OR:1.64;95%CI:1.25 to 2.16), were more likely to be symptomatic when infected with SARS-CoV-2. Pregnant women with Black (OR:1.48;95%CI:1.19 to 1.85) or Asian (OR:1.64;95%CI:1.23 to 2.18) ethnicity were more likely to be symptomatic while those with White ethnicity (OR:0.63;95%CI:0.52 to 0.76) were more likely to be asymptomatic. Cesarean-section delivery (OR:1.40;95%CI:1.17 to 1.67) was more likely amongst symptomatic pregnant women. The mean birthweight(g) (MD:240.51;95%CI:188.42 to 293.51), was significantly lower, while the odds of low birthweight (OR:1.85;95%CI:1.06 to 3.24) and preterm birth (< 37 weeks) (OR:2.10;95%CI:1.04 to 4.23) was higher amongst symptomatic pregnant women. Symptomatic pregnant women had a greater requirement for maternal ICU admission (OR:13.25;95%CI:5.60 to 31.34) and mechanical ventilation (OR:15.56;95%CI:2.96 to 81.70) while their neonates had a higher likelihood for Neonatal Intensive Care Unit admission (OR:1.96;95%CI:1.59 to 2.43). The management strategies in the included studies were poorly discussed, hence could not be analyzed. Conclusion The evidence suggests that the presence of risk factors (co-morbidities and ethnicity) increased the likelihood of pregnant women being symptomatic. Higher odds of complications were also observed amongst symptomatic pregnant women. However, more adequately conducted studies with adjusted analysis and parallel comparison groups are required to reach conclusive findings.


2020 ◽  
Author(s):  
Md Ziaul Islam ◽  
Tasnim Disu ◽  
Shatmin Farjana ◽  
Mohammad Rahman

Abstract Background: Malnutrition and depression are highly prevalent in the elderly and can lead to disparaging outcomes. Analytical studies on malnutrition concerning geriatric depression (GD) are very scarce in Bangladesh, although the size of the elderly population is increasing fast in the country. The current study aimed to assess the association between malnutrition and depression and associated risk factors in the rural elderly.Methods: A case-control study was conducted in 600 elderly residents (aged ≥60 years) of three rural communities of Bangladesh from January to October 2019. Three hundred depressed elderly people were enrolled as cases and 300 non-depressed elderly individuals were included as community controls by matching the age and living area of the cases. We used a semi-structured questionnaire based on the Geriatric Depression Scale-15 and the Bangla version of Mini-Nutritional Assessment-Short Form to collect data through face-to-face interviews. Measures included baseline and personal characteristics, malnutrition, GD, and associated risk factors. A binary logistic regression model was fitted to identify variables associated with the risk of GD.Results: The study found no significant difference in gender (male Vs. female) between cases (44.0% Vs. 56.0%) and controls (46.0% Vs. 54.0%). The study revealed that malnutrition was significantly (p<0.01) higher in cases (56.0%) than in controls (18.0%). The malnourished elderly had around three times AOR=3.155; 95% CI: 1.53-6.49, p=0.002) more (risk of having depression than the controls. The unemployed elderly (AOR=4.964; 95% CI: 2.361-10.440; p=0.0001) and the elderly of the lower and middle class (AOR=3.654; 95% CI: 2.266-7.767; p=0.001) were more likely to experience depression. The elderly having a poor diet were more likely to experience depression (AOR=3.384; 95% CI: 1.764-6.703; p=0.0001). The single elderly (AOR=2.368; 95% CI: 1.762-6.524; p=0.001) and the elderly tobacco users (AOR=2.332; 95% CI: 1.663-5.623; p=0.003) were more likely to experience depression.Conclusions: A significant association between malnutrition and depression is evident in the rural elderly individuals of Bangladesh. It will be a prolific initiative if policymakers merge malnutrition and the risk factors associated with geriatric depression in the provision of universal health care for better health and well-being of the rural elderly populations.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amos Gyamfi ◽  
Charles Brown ◽  
Samuel Antwi-Baffour

Abstract Objectives The aim of the study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of selected genes (β3-adrenergic receptors-ADRB3, Leptin receptor-LEPR, Peroxisome proliferator activator receptor γ-PPARG) and obesity among Ghanaian adults. Methods This was a case-control study comprising 24 cases of newly diagnosed obese; BMI ≥30 kg/m2, at the Dietherapy Unit of the Korle-Bu Teaching Hospital (KBTH), and 32 controls of non-obese staff and clinical students at KBTH. A validated questionnaire was used for demographic, dietary and anthropometric data. Dietary intake was assessed using a food frequency questionnaire, and DNA extracted from mouth rinse water samples. SNPs in the ADRB3, LEPR and PPARG genes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR –RFLP). Results There were statistically significant differences in BMI, WHR and MUAC measurements between cases and controls (all p s˂ 0.0001). There was no statistically significant difference (P = 0.3032) between the mean energy intakes of both cases and controls. DNA fragments for the PPARG gene was amplified in 55 respondents. No relationship was observed between PPARG (Pro12Pro) SNP and BMI, MUAC and WHR among participants. Amplification was successful in 19 cases and 24 controls for ADRB3 (Trp64Trp & Trp64Arg). No significant difference (all ps > 0.05) emerged for the ADRB3 SNPs frequencies between the cases and the controls for BMI, MUAC and WHR. LEPR amplification was successful in 15 cases and 14 controls. Amplicons of six cases, all in the OBClass 1 to OBClass 3 range, indicated the presence of the Gln223Arg SNP after RFLP. A significant difference (all ps < 0.05) emerged for LEPR (Gln223Arg) SNP frequencies between the cases and the controls for BMI, MUAC and WHR. Conclusions There were no observed relationships among ADRB3, PPARG SNPs and BMI, MUAC and WHR. LEPR (Gln223Arg) SNP was statistically associated with BMI, MUAC and WHR. Funding Sources 1. College of Health Sciences, University of Ghana Research Grant for MSc/MPhil Thesis/Dissertation. 2. Self funding.


Cephalalgia ◽  
2008 ◽  
Vol 28 (5) ◽  
pp. 553-557 ◽  
Author(s):  
K Biehl ◽  
A Frese ◽  
M Marziniak ◽  
I-W Husstedt ◽  
S Evers

To investigate the possible association between migraine and left-handedness, we enrolled 100 patients with a diagnosis of migraine according to the International Headache Society diagnostic criteria and 100 age- and sex-matched control subjects into a case—control study. Handedness was determined by the Edinburgh Handedness Inventory. There was no significant difference in the frequency or grade of left-handedness between the two groups. Additionally, we pooled our data with those from five similar studies, which did not alter the result. Thus, neither our study nor the meta-analysis support Geschwind and Behan's hypothesis of an association between migraine and left-handedness.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2601-2601
Author(s):  
Karine Lacut ◽  
Gregoire Le Gal ◽  
Emmanuel Oger ◽  
Dominique Mottier

Abstract Background: Preliminary reports suggest that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism (VTE), but others did not confirm these results. Objective: To evaluate the relationship between antipsychotic drugs and VTE. Design: Case-control study (EDITH) designed to investigate genetic and environmental risk factors of VTE. Setting: Brest University Hospital. Participants: 857 patients consecutively hospitalized for a documented venous thromboembolic event were included between May 2000 and May 2004. Controls were matched on age, sex and the main risk factors of venous thromboembolism (cancer, surgery, pregnancy…). Results: The mean age of patients was 67.7 year. No significant difference was found between cases and controls concerning the main characteristics, except for smocking and body mass index. Among cases, 89 (10.4%) were current users of neuroleptics compared to 35 (4.8%) among controls. Current use of neuroleptics was associated with a significant increased risk of venous thromboembolism (OR = 2.32, 95% CI: 1.55–3.48). Excluding neuroleptics used for non psychiatric disorders, and after adjustment on the main confounding factors, this association remained significant (OR = 3.48, 95% CI: 2.00–6.04). No difference was found between the different chemical categories of neuroleptics, but the number of patients in some groups had limited statistical power to demonstrate significant differences. Biological mechanisms of action have been proposed to explain this relation. Analyses are ongoing for anti-phospholipid antibodies and homocysteine. Conclusion: In this case-control study of hospitalized patients, neuroleptics use was associated with a significant increased risk of venous thromboembolism. These results are concordant with previous reports. Nevertheless, further investigations are needed to explain wich mechanisms may be involved in such association and before use of neuroleptics can be definitely considered as risk factor for venous thromboembolism.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ni ◽  
Anlai Ji ◽  
Junfeng Yin ◽  
Xiangjun Wang ◽  
Xinnong Liu

Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk.Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI).Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model.Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.


2020 ◽  
Author(s):  
Guoxiang Rong ◽  
Yongping Zhu ◽  
Weifeng Tang ◽  
Hao Qiu ◽  
Sheng Zhang

The relationship between rs3746444 T&gt;C single nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1,476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T&gt;C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3,954 GC cases and 9,745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P = 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P&gt;0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.


2018 ◽  
Vol 1 ◽  
pp. 1 ◽  
Author(s):  
James Abugri ◽  
Felix Ansah ◽  
Kwaku P. Asante ◽  
Comfort N. Opoku ◽  
Lucas A. Amenga-Etego ◽  
...  

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) and the antifolate drug sulfadoxine-pyrimethamine (SP) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we genotyped single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter (pfcrt, PF3D7_0709000), multidrug resistance (pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase (pfdhfr, PF3D7_0417200) and dihydropteroate synthase (pfdhps, PF3D7_0810800) genes in children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) between 2012 and 2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10% and 65% of infections respectively. Most of the isolates harboured the antifolate resistance-associated pfdhfr 51I, 59R and 108N alleles, including 68% of them with the triple mutant pfdhfr I51R59N108 combination. Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra than at the other sites. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I51R59N108/G437). Conclusion: Comparison of the present results to previously published data shows a significant decrease in the prevalence of CQ resistance alleles during the 12 years after CQ withdrawal, but an increase in the alleles that mediate SP resistance, which could be due to the continuous use of antifolate drugs for prophylaxis.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 419
Author(s):  
Azharuddin Azharuddin ◽  
Muhammad Ilmawan ◽  
Jonny Karunia Fajar ◽  
Marhami Fahriani ◽  
Sukamto S. Mamada ◽  
...  

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL-1A), tumor necrosis factor-alpha (TNF-A), and vitamin D receptor (VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.


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