The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

Cephalalgia ◽  
2015 ◽  
Vol 36 (7) ◽  
pp. 615-623 ◽  
Author(s):  
Ann-Louise Esserlind ◽  
Anne Francke Christensen ◽  
Stacy Steinberg ◽  
Niels Grarup ◽  
Oluf Pedersen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Single Nucleotide Polymorphisms ◽  
Case Control ◽  
Control Group ◽  
Control Analysis ◽  
Nucleotide Polymorphisms ◽  
Susceptibility Loci ◽  
Single Nucleotide ◽  
Severe Migraine

Introduction The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population. Methods Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model. Results We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks. Conclusion Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.

scholarly journals Association of DEAR1 Tagging Single Nucleotide Polymorphisms With Breast Cancer in a Sample of Colombian Population: A Case Control Study

2020 ◽  
Vol 14 ◽  
pp. 117822342090493
Author(s):  
Angela P Beltrán ◽  
Edgar Benitez ◽  
Martin Rondon ◽  
Yeimy V Ariza ◽  
Fabio A Aristizabal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Single Nucleotide Polymorphisms ◽  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Control Study

Purpose: Ubiquitin ligase genes can act as oncogenes or tumor suppressor genes. They play a role in various diseases, including development and progression of breast cancer; the objective of this study was to evaluate the association of common variants in the ductal-epithelium-associated RING chromosome 1 ( DEAR1) gene with breast cancer risk in a sample of Colombian population. Methods: We carried out a case-control study to investigate associations of variants in DEAR1 with breast cancer in women from Colombia. Single nucleotide polymorphisms (SNPs) rs584298, rs2927970, rs59983645, and rs599167 were genotyped in 1022 breast cancer cases and 1023 healthy controls using the iPLEX® and Kompetitive Allele Specific PCR (polymerase chain reaction) (KASP) method. The associations between SNPs and breast cancer were examined by conditional logistic regression. The associations between SNPs and epidemiological/histopathological variables were examined by multinomial logistic regression. Results: Associations were found between tag SNPs and breast cancer adjusted for the epidemiological risk factors rs584298 genotypes AG and GG ( P = .048 and P = .004, respectively). The analysis of the disease characteristics showed that SNP rs584298 (genotype AG) ( P = .015) shows association with progesterone receptor (PR) status and (genotype AA) ( P = .048) shows association with human epidermal growth factor receptor 2 (HER2) status. Conclusions: The SNP rs584298 in DEAR1 showed associations with breast cancer and the expression of HER2 receptor; when this receptor is amplified, the result is aggressive tumoral subtype and expression of PR receptor that is associated with high-proliferative tumor grade. Validation of this SNP is important to establish whether this variant or the tagged variant is the cause for the risk association showed.

scholarly journals Strong association of tissue inhibitor of metalloproteinase (TIMP)-2 and -3 promoter single nucleotide polymorphisms with risk of colorectal cancer in ethnic Kashmiri population – a case control study

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Mujeeb Zafar Banday ◽  
Aga Syed Sameer
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Tumor Invasion ◽  
Case Control ◽  
Nucleotide Polymorphisms ◽  
Heterozygous Genotype ◽  
Single Nucleotide ◽  
Promoter Snps ◽  
Kashmiri Population

Abstract Background: The tissue inhibitors of metalloproteinases (TIMPs) including TIMP2 and TIMP3 are the key physiological inhibitors of matrix metalloproteinases (MMPs) and along with MMPs, TIMPs play a vital role in the coordinated proteolytic breakdown and remodeling of the extracellular matrix (ECM) and the basement membrane that represent the barriers to any malignant tumor invasion and progression. These enzymes are vital for tumor invasion and metastasis and also play a critical role in several other stages of tumor development and progression. The studies on the association of various polymorphisms in human TIMP2 and TIMP3 genes including TIMP2-418G/C and TIMP3-1296T/C single nucleotide polymorphisms (SNPs) and CRC risk are limited, mixed, and inconclusive. Materials and methods: The aim of the present study was to analyze the association of TIMP2-418G/C and TIMP3-1296T/C promoter SNPs with colorectal cancer (CRC) susceptibility and development risk and also to evaluate the modifying effects of possible TIMP2-418G/C and TIMP3-1296T/C SNPs’ genotypes on different risk factors of CRC or the reciprocal effect in ethnic population of Kashmir, India through a case–control setup. The genotype frequencies of TIMP2-418G/C and TIMP3-1296T/C promoter SNPs were compared between 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the TIMP2-418G/C and TIMP3-1296T/C SNPs and CRC risk were examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. The possible effect measure modification of the association between the relevant SNP genotypes and CRC risk by various CRC risk factors including age, gender, and smoking status was also analyzed. Further, the associations between these SNPs and various clinico-pathological parameters, demographic variables, and environmental factors within the case group subjects with regard to CRC risk were also evaluated. Results: The overall association between the TIMP2-418G/C and TIMP3-1296T/C SNPs and the modulation of CRC risk was found to be highly significant (P=0.019 and P=0.000 for TIMP2 and TIMP3 SNPs, respectively). The heterozygous genotype (GC) of TIMP2-418G/C was significantly associated with an increased risk of colorectal cancer [OR, 1.87 (95%CI, 1.07–3.27); P=0.027] whereas the heterozygous genotype (TC) of TIMP3-1296T/C SNP was significantly associated with a decreased risk of colorectal cancer [OR, 0.53 (95%CI, 0.32–0.86); P=0.011]. The variant genotype (CC) of TIMP3-1296T/C SNP was also significantly associated with a decreased risk of colorectal cancer [OR, 0.18 (95%CI, 0.05–0.65); P=0.009]. Conclusion: The present study demonstrates that there is a strong and highly significant association between the TIMP2-418G/C and TIMP3-1296T/C promoter SNPs and the risk of developing CRC in ethnic Kashmiri population. However, in order to substantiate our findings, the present study needs to be replicated with bigger sample size and should involve other ethnically defined populations with high CRC risk.

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

scholarly journals Association between CTSS gene polymorphism and the risk of acute atherosclerotic cerebral infarction in Chinese population: a case–control study

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Lian Luo ◽  
Mingli Zhu ◽  
Jiajun Zhou
Keyword(s):  
Cerebral Infarction ◽  
Case Control Study ◽  
Case Control ◽  
Cathepsin S ◽  
Control Group ◽  
Study Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Independent Risk Factors ◽  
Control Study

Objective: To investigate the association between the gene polymorphisms of rs774320676, rs768437857, rs928508030, and rs2275235 loci of Cathepsin S (CTSS) and risk of acute atherosclerotic cerebral infarction. Methods: A total of 315 patients with acute atherosclerotic cerebral infarction (study group) and 220 healthy subjects (control group) were enrolled in the present study. The genetic polymorphism of rs774320676, rs768437857, rs928508030, and rs2275235 loci of CTSS of subjects was analyzed by PCR-Sanger sequencing. Results: The proportion of carriers with mutant T allele at rs774320676 locus and mutant G allele at rs928508030 locus of CTSS in study group was significantly higher than the proportion in control group (P=0.000, adjusted odds ratio (OR) = 1.332, 95% confidence interval (CI) = 1.200–1.460; P<0.001, adjusted OR = 1.185, 95% CI = 1.055–1.314; P=0.002). The T allele at rs774320676 locus and the G allele at rs928508030 locus of CTSS were independent risk factors for acute atherosclerotic cerebral infarction (OR = 2.534, 95% CI = 1.020–4.652, P=0.006; OR = 2.016, 95% CI = 1.031–4.385, P=0.031). Conclusion: The single nucleotide polymorphisms (SNPs) of rs774320676 and rs928508030 of CTSS gene were related with risk for acute atherosclerotic cerebral infarction. The T allele at rs774320676 locus and G allele at rs928508030 locus of CTSS were genetic susceptibility genes of acute atherosclerotic cerebral infarction.

scholarly journals Genotyping of Essential Hypertension Single-Nucleotide Polymorphisms by a Homogeneous PCR Method with Universal Energy Transfer Primers

2002 ◽  
Vol 48 (12) ◽  
pp. 2131-2140 ◽  
Author(s):  
Chikh Bengra ◽  
Theodore E Mifflin ◽  
Yuri Khripin ◽  
Paolo Manunta ◽  
Scott M Williams ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Single Nucleotide Polymorphisms ◽  
Restriction Endonucleases ◽  
Control Group ◽  
Italian Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hypertensive Patients ◽  
Unique Restriction ◽  
Set Up

Abstract Background: Human hypertension is a complex, multifactorial disease with a heritability of more than 30–50%. A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management. Methods: Tailed allele-specific primers were designed to amplify by PCR six biallelic SNP loci [three in G protein-coupled receptor kinase type 4 (GRK4): R65L, A142V, and A486V; two in angiotensinogen: −6G→A and M235T; and one in aldosterone synthase: −344C→T] associated with essential hypertension. PCRs of SNP loci were coupled (via a common sequence of 21 nucleotide tails) to incorporate Universal Amplifluor™ primers labeled with fluorescein or sulforhodamine in a homogeneous format. Use of Amplifluors in SNP PCRs produced labeled amplicons, the fluorescence of which was quantified by a microplate reader and then analyzed via an Excel macro to provide genotypes for all six SNP loci. Unique restriction endonucleases were identified for five SNP loci that could independently confirm homogeneous PCR results when needed. Results: We developed six homogeneous PCR assays that were set up, performed, and fluorometrically analyzed in 96-well microplates. Allele frequencies were determined for six SNPs in 60 Italian hypertensive patients and a control group of 60 normotensive persons. A significant correlation (P = 0.034) between one SNP [GRK4 (A486V)] and the hypertensive patients was observed. Genotyping results for five of six SNPs were confirmed by digesting corresponding amplicons with locus-specific restriction endonucleases. Conclusions: We developed a simple and homogeneous fluorescent protocol that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons. We also observed a significant association (P = 0.034) between one SNP (A486V) and an Italian population of mildly hypertensive patients.

scholarly journals Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

2021 ◽  
Vol 48 (1) ◽  
pp. 69-79
Author(s):  
Amer Mahmoud Sindiani ◽  
Osamah Batiha ◽  
Esra’a Al-zoubi ◽  
Sara Khadrawi ◽  
Ghadeer Alsoukhni ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Statistical Significance ◽  
Ovarian Response ◽  
Control Group ◽  
P Value ◽  
Case Group ◽  
Nucleotide Polymorphisms ◽  
Poor Ovarian Response ◽  
Single Nucleotide ◽  
Number Of Patients

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

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