scholarly journals Comparison of SNP Genotypes Related to Proliferative Vitreoretinopathy (PVR) across Slovenian and European Subpopulations

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Xhevat Lumi ◽  
Mateja M. Jelen ◽  
Daša Jevšinek Skok ◽  
Emanuela Boštjančič ◽  
Metka Ravnik-Glavač ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Association Studies ◽  
Case Control ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Case Control Studies ◽  
Ensembl Database ◽  
Functional Polymorphisms ◽  
Genotype Frequencies ◽  
Frequency Changes

The present study investigated the distribution of genotypes within single nucleotide polymorphisms (SNPs) in genes, related to PVR pathogenesis across European subpopulations. Genotype distributions of 42 SNPs among 96 Slovenian healthy controls were investigated and compared to genotype frequencies in 503 European individuals (Ensembl database) and their subpopulations. Furthermore, a case-control status was simulated to evaluate effects of allele frequency changes on statistically significant results in gene-association studies investigating functional polymorphisms. In addition, 96 healthy controls were investigated within 4 SNPs: rs17561 (IL1A), rs2069763 (IL2), rs2229094 (LTA), and rs1800629 (TNF) in comparison to PVR patients. Significant differences (P<0.05) in distribution of genotypes among 96 Slovenian participants and a European population were found in 10 SNPs: rs3024498 (IL10), rs315952 (IL1RN), rs2256965 (LST1), rs2256974 (LST1), rs909253 (LTA), rs2857602 (LTA), rs3138045 (NFKB1A), rs3138056 (NFKB1A), rs7656613 (PDGFRA), and rs1891467 (TGFB2), which additionally showed significant differences in genotype distribution among European subpopulations. This analysis also showed statistically significant differences in genotype distributions between healthy controls and PVR patients in rs17561 of the IL1A gene (OR, 3.00; 95% CI, 0.77–11.75; P=0.036) and in rs1800629 of the TNF gene (OR, 0.48; 95% CI, 0.27–0.87; P=0.014). Furthermore, we have shown that a small change (0.02) in minor allele frequency (MAF) significantly affects the statistical p value in case-control studies. In conclusion, the study showed differences in genotype distributions in healthy populations across different European countries. Differences in distribution of genotypes may have had influenced failed replication results in previous PVR-related SNP-association studies.

Association of MDM2 Gene Polymorphisms SNP285 and 309 with Myelodysplastic Syndromes (MDS) Susceptibility and Outcome.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2823-2823
Author(s):  
Kathy L. McGraw ◽  
Lan Min Zhang ◽  
William Fulp ◽  
Hui-Yi Lin ◽  
Andres Jerez ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Response Rate ◽  
Disease Onset ◽  
Response Duration ◽  
Negative Regulator ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 2823 Background: Mutations in TP53, or less often its regulators, increases risk for malignant transformation. Murine double minute protein 2 (MDM2), an E3 ubiquitin ligase, targets p53 for proteasomal degradation and is the most well studied negative regulator of p53. Recent investigations have highlighted the emerging importance of p53 in MDS. Haploinsufficiency for ribosomal protein S14 in deletion 5q MDS liberates free ribosomal proteins that bind to and promote degradation of MDM2, thereby activating p53 in erythroid precursors. A single nucleotide polymorphism (SNP) in an MDM2 promoter (SNP309) is linked to younger age of onset of several solid tumors and an increased risk for acute myeloid leukemia (AML) [Knappskog and Lonning. 2011. Transcription 2:207, Xiang et al. 2009. Leuk Res. 33:1454]. The thymine (T) to guanine (G) substitution introduces an additional Sp1 transcription factor binding site causing upregulation of MDM2 transcription. A second SNP in this promoter (SNP285) has also been linked to cancer susceptibility, where a guanine (G) to cytosine (C) exchange is associated with decreased ovarian and breast cancer risk (Knappskog and Lonning. 2011. Oncotarget. 2:251). The C-allele of SNP285 has diminished Sp1 promoter binding compared to the G-allele decreasing MDM2 expression. In this study we investigated genotype distribution of MDM2 SNPs in del(5q) and non-del(5q) MDS patients and compared results to healthy controls. Methods and Results: Using Sanger sequencing, we compared allele and genotype frequencies for SNP285 and SNP309 in 155 healthy controls, 97 non-del(5q), and 119 del(5q) MDS patients. For SNP285, we found no significant difference in genotype or allele frequency among non-del(5q) or del(5q) cases compared to controls (p=0.25 and 0.26, respectively). Although there was no difference in age at diagnosis by genotype in del(5q) MDS (p=0.82), there was a significant difference among non-del(5q) MDS cases [p<0.01, mean (range) for GC:80.8y (75–89) and GG:68.9y (27–91)], however, the frequency of the GC genotype was low [n=5, non-del(5q); n=11, del(5q)] with no CC genotype cases. For SNP309, there was no difference in allele frequency (p=0.68), however genotype frequency differed between controls, non-del5q, and del5q MDS (p=0.06). The genotype distribution was significantly different between non-del(5q) and del(5q) MDS (p=0.01). SNP309 genotype frequencies for controls, non-del(5q), and del(5q) MDS were GG:17.3%, 22.7%, 10.1%; TG: 42.9%, 37.1%, 53.8%; TT: 39.7%, 40.2%, 36.1%, respectively. We found no difference in age of disease onset by SNP309 genotype in either non-del(5q) or del(5q) cases (p=0.08 and 0.97, respectively). There was no significant relationship between SNP285 genotype and IPSS (p=1.0), cytogenetic risk (p=0.66), or WHO classification (p=0.16) in non-del(5q) or del(5q) cases (p=1.0, 0.78, and 0.60, respectively). Similar results were observed for SNP309 [p=0.85, 0.39, and 0.68 for non-del(5q); p= 0.06, 0.98, 0.27 for del(5q), respectively]. For SNP285 there was no difference in overall survival (OS) by genotype in either non-del(5q) (p=0.65) or del(5q) MDS (p=0.72). Progression free survival (PFS) also did not differ by genotype in non-del(5q) (p=0.82) or del(5q) (p=0.58) patients. There was a significant difference in LEN response rate in del(5q) MDS (p=0.04, non-responders: 23.8% GC and 76.2% GG, responders: 4.9% GC and 95.1% GG), however, genotype did not influence response duration (p= 0.40). For SNP309, there were no significant difference in OS by genotype (p=0.42), PFS (p=0.78), LEN response rate (p=0.17), or response duration in del(5q) MDS (p=0.65). In non-del(5q), there was no difference in OS (p=0.42), LEN response rate (p=0.91), or response duration (p=0.47). However, we found a significant difference in PFS by genotype (p=0.03) with more prolonged PFS in patients with the heterozygous TG genotype (60 mo PFS: GG 55.3%, TT 54.1%, and TG 81.7%). Finally, we found no difference in chromosome 5 deletion size or deletion location in del(5q) MDS according to SNP309 genotype. Conclusions: MDM2 SNP309 may be linked to MDS susceptibility, as well as LEN responsiveness and PFS in del(5q) and non-del(5q) MDS, respectively. These data warrant validation in a larger patient cohort. Investigation of the interaction between MDM2 SNPs and the well described TP53 R72P SNP is underway. Disclosures: List: Celgene: Consultancy.

scholarly journals p.Arg72Pro polymorphism of P53 and Breast Cancer Risk: A meta-analysis of case-control studies

2020 ◽  
Author(s):  
Brehima Diakite ◽  
Yaya Kassogue ◽  
Guimogo Dolo ◽  
Jun Wang ◽  
Erin Neuschler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Additive Model ◽  
P53 Gene ◽  
Case Control ◽  
Additive Models ◽  
Case Control Studies ◽  
Genotype Frequencies

Abstract Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cases age-matched controls including7841disease cases and 8876controls were evaluated in this meta-analysis. Overall, our results suggested that p.Arg72ProP53 was associated with a risk for breast cancer for the dominant model (OR= 1.09, 95% CI = 1.02-1.16; P= 0.01) and the additive model (OR= 1.09, 95% CI = 1.01-1.17; P= 0.03), but not in the recessive model (OR = 1.07, 95% CI = 0.97-1.16; P= 0.19). According to the ethnic group, allele Pro has been associated with breast cancer risk in Europeans for the dominant and additive models. Conclusions : This meta-analysis found a significant association between p.Arg72Pro in the P53 gene and the risk of breast cancer. Individuals carrying at least one Pro allele of the P53 gene are more likely to have breast cancer with dominant and additive models than individualsharboringthe Arg allele.

scholarly journals Estrogen receptor alpha gene polymorphisms in patients with late onset Alzheimer’s disease

Genetika ◽  
2014 ◽  
Vol 46 (2) ◽  
pp. 437-444 ◽  
Author(s):  
Nasim Sohrabifar ◽  
Jalal Gharesouran ◽  
Mahnaz Talebi ◽  
Morteza Ghojazadeh ◽  
Ardebili Mohaddes
Keyword(s):  
Estrogen Receptor ◽  
Late Onset ◽  
Case Control ◽  
Estrogen Signaling ◽  
Control Group ◽  
Additional Risk Factor ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Estrogen Receptor Alpha Gene ◽  
Disease Case

Evidences have been gathered from several studies suggest that a mechanism involving an estrogen-signaling pathway may contribute to modulate risk for Alzheimer?s disease. It was demonstrated that estrogen up-regulates the expression of apolipoprotein E gene, which has a role in the metabolism of b-amyloid that is related to the progress of Alzheimer?s disease. Case-control studies have found an increased frequency of PvuII and XbaI polymorphisms in affected subjects. In this study we explore the possible association of different polymorphic forms of human a-estrogen receptor (ER- a) with the risk to late onset Alzheimer?s disease in north-west Iranian population. We conducted a case-control study in a dataset of 160 LOAD patients and 163 healthy controls that have been matched in gender and age. To evaluate the PvuII and XbaI polymorphisms in Alzheimer?s disease we used PCR/RFLP method and genotype frequencies were statistically determined. The PCR products prepared from 21 AD cases and 20 healthy controls were randomly purified by ethanol precipitation and bidirectionally sequenced. The frequency of normal and mutated alleles for PvuII and XbaI locuses respectively, in the LOAD group were significantly higher than those in the control group (P<0.001, OR=0.51, 95 % CI 0.35-0.74 for XbaI locus; P<0.001, OR=0.41, 95 % CI 0.3-0.57 for PvuII locus). This result suggests that ER? XbaI and PvuII polymorphism is an additional risk factor for late-onset Alzheimer?s disease.

scholarly journals Healthy Controls Are Not Appropriately Identified for Comparison to Irritable Bowel Syndrome in Case Control Studies

2011 ◽  
Vol 140 (5) ◽  
pp. S-799 ◽  
Author(s):  
Shireen Ghorbani ◽  
Amir Nejad ◽  
David Law ◽  
Kathleen Chua ◽  
Meridythe M. Amichai ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Case Control ◽  
Healthy Controls ◽  
Case Control Studies ◽  
Irritable Bowel

scholarly journals  Allele frequency in loci which control coat colours in Hucul horse population

2012 ◽  
Vol 57 (No. 4) ◽  
pp. 178-186 ◽  
Author(s):  
A. Stachurska ◽  
A. Brodacki ◽  
J. Grabowska
Keyword(s):  
Genetic Structure ◽  
Allele Frequency ◽  
Global Strategy ◽  
Recessive Allele ◽  
Genotype Distribution ◽  
Horse Population ◽  
Wahlund Effect ◽  
Animal Genetic Resources ◽  
Genotype Frequencies ◽  
Its Gene

The objective of the study was to determine the frequency of alleles which produce coat colours in Hucul horse population in Poland. The breed is included in the Global Strategy for Management of Farm Animal Genetic Resources, hence its gene pool should remain in unaltered state. Huculs are bay, black, blue dun, yellow dun, tobiano, and chestnut. Grey and chestnut Huculs have always been undesirable. The material consisted of all 1022 matings which resulted in subpopulations recorded in Studbook volumes. The recessive allele frequency was estimated as the square root of recessive genotype frequencies in ASIP (A), MC1R (E), DUN (D), KIT (To region), and STX17 (G) loci. The frequency in A and E loci in total parental generation was also estimated in test matings. Genotype distribution in the population was anticipated according to gamete frequency in sires and dams. Small Wahlund effect, F<sub>ST</sub>and &chi;<sup>2</sup> values for allele distributions show that division into subpopulations did not influence the population genetic structure significantly. Mean recessive allele frequency in A, E, D, To, and G loci amounted to 0.521, 0.115, 0.878, 0.929, and 0.997, respectively, and in A and E loci it was similar to that assessed in test matings. More bay horses and fewer D diluted horses appeared in offspring than expected. A, e, d, and To allele frequency showed a rising tendency. The genetic structure in Hucul population is not constant and does not comply strictly with the preservation aim. Bay, non-diluted, and tobiano horses are preferred. The linkage between MC1R and KIT loci can make the selection against e allele difficult. Breeders&rsquo; preferences may lead to undesired changes in the allele frequency. To avoid such risk, it is recommended to select horses strictly complying with the rules included in the breeding programme and mate the horses randomly from this aspect. &nbsp;

Association between Transforming Growth Factor Alpha TaqI Polymorphism and Susceptibility to the Nonsyndromic Cleft Lip and/or Palate in an Iranian Population: A Case Control Study

2020 ◽  
Author(s):  
Abdolhamid Amooee ◽  
Seyed Mohammadreza Niktabar ◽  
Mohammad Javad Akbarian-Bafghi ◽  
Majid Morovati-Sharifabad ◽  
Mohamad Hosein Lookzadeh ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Cleft Lip ◽  
Case Control Study ◽  
Transforming Growth Factor ◽  
Case Control ◽  
Iranian Population ◽  
Case Control Studies ◽  
Increased Risk ◽  
Significant Difference ◽  
Control Study

Background: The TGF-α TaqI C >T polymorphism is a well-characterized variant for nonsyndromic cleft lip and/or palate (NS CL/P), but it has shown inconsistent results of association with nonsyndromic CL/P across a number of studies. Thus, we have performed this case-control study to clarify the association between the TGF-α TaqI C >T polymorphism and NS CL/P risk.   Methods: One-hundred ten cases with NSCL/P and 110 controls were recruited to the current study. We have genotyped the TGF-α TaqI C >T polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The odds ratio (OR) and 95% confidence interval (CI) were applied for strength of association TGF-α TaqI C >T polymorphism with NSCL/P.   Results: The TGF-α TaqI C >T polymorphism CC, CT and TT genotypes frequencies in the NSCL/P cases were 30.9%, 57.3% and 11.8%, respectively while the corresponding frequencies in the controls were 37.3%, 52.7% and 10.0%, respectively. The frequency of C and T alleles in the case were 59.5% and 40.5%, respectively while the corresponding allelic frequencies in the controls were 63.6% and 36.4%. There was no significant difference in the genotype and allele frequency for TGF-α TaqI C >T polymorphism between cases and controls. The minor allele frequency (MAF) of TGF-α TaqI C >T polymorphism among healthy controls was 0.36.   Conclusion: Our study indicates that the TGF-α TaqI C>T polymorphism was not significantly associated with increased risk of NS CL/P in the Iranian population. However, our results still need to be confirmed by further large and well-designed case-control studies.

scholarly journals Transcriptionally Less Active Prodynorphin Promoter Alleles are Associated with Temporal Lobe Epilepsy: A Case-Control Study and Meta-Analysis

2008 ◽  
Vol 24 (3) ◽  
pp. 135-140 ◽  
Author(s):  
Marcelo A. Kauffman ◽  
Damián Consalvo ◽  
Moron Dolores Gonzalez ◽  
Silvia Kochen
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Fixed Effects ◽  
Association Studies ◽  
Hippocampal Sclerosis ◽  
Meta Analysis ◽  
Case Control ◽  
Healthy Controls ◽  
Fixed Effects Model ◽  
Familial Predisposition

We performed an association study in a population of patients with Mesial Temporal Lobe Epilepsy (TLE) with Hippocampal Sclerosis (MTEHS) together with a systematic revision of the literature to investigate the role of transcriptionally less active polymorphic alleles of Prodynorphin (PDYN) gene in this pathology. We included 102 patients with a diagnosis of MTEHS and 86 healthy controls. The positive antecedent of family history for epileptic events defined a TLE subgroup with familial predisposition for epileptic disorders. The PDYN promoter polymorphism was genotyped by means of a PCR assay. For meta-analysis, we identified case-control association studies between TLE and PDYN by searching PUBMED. The pooled OR was estimated using a fixed effects model under dominant and co-dominant heredity models. No differences in genotypic and allelic frequencies were found between cases and controls (p= 0.61) in our population, neither in the whole cohort nor in the analysis limited to TLE with familial predisposition (p= 0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p= 0.003; OR = 1.40; IC 95 = 1.12–1.74) and a modestly higher risk to develop TLE in the group of patients with familial predisposition. Therefore, functional allelic variants in the PDYN promoter might modify the risk to develop TLE in subjects with familial predisposition.

scholarly journals Simple F Test Reveals Gene-Gene Interactions in Case-Control Studies

2012 ◽  
Vol 6 ◽  
pp. BBI.S9867 ◽  
Author(s):  
Guanjie Chen ◽  
Ao Yuan ◽  
Jie Zhou ◽  
Amy R. Bentley ◽  
Adebowale Adeyemo ◽  
...  
Keyword(s):  
Complex Disease ◽  
Association Studies ◽  
Parametric Method ◽  
Case Control ◽  
Gene Interactions ◽  
Ratio Test ◽  
Genome Wide Association Studies ◽  
Case Control Studies ◽  
F Test ◽  
Howard University

Missing heritability is still a challenge for Genome Wide Association Studies (GWAS). Gene-gene interactions may partially explain this residual genetic influence and contribute broadly to complex disease. To analyze the gene-gene interactions in case-control studies of complex disease, we propose a simple, non-parametric method that utilizes the F-statistic. This approach consists of three steps. First, we examine the joint distribution of a pair of SNPs in cases and controls separately. Second, an F-test is used to evaluate the ratio of dependence in cases to that of controls. Finally, results are adjusted for multiple tests. This method was used to evaluate gene-gene interactions that are associated with risk of Type 2 Diabetes among African Americans in the Howard University Family Study. We identified 18 gene-gene interactions ( P < 0.0001). Compared with the commonly-used logistical regression method, we demonstrate that the F-ratio test is an efficient approach to measuring gene-gene interactions, especially for studies with limited sample size.

scholarly journals A review of HLA and COVID-19 association studies

2020 ◽  
Vol 3 (2) ◽  
pp. 25-30
Author(s):  
Renata Zunec
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Human Leukocyte ◽  
Genetic System ◽  
Epidemiological Studies ◽  
Population Based ◽  
Case Control ◽  
Case Control Studies ◽  
First Case ◽  
Scale Population

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is reported to vary across different populations in the prevalence of infection, in the death rate of patients, in the severity of symptoms and in the drug response of patients. Among host genetic factors that can influence all these attributes human leukocyte antigen (HLA) genetic system stands out as one of the leading candidates. Case-control studies, large-scale population-based studies, as well as experimental bioinformatics studies are of utmost importance to confirm HLA susceptibility spectrum of COVID-19. This review presents the results of the first case-control and epidemiological studies performed in several populations, early after the pandemic breakout. The results are pointing to several susceptible and protective HLA alleles and haplotypes associations with COVID-19, some of which might be of interest for the future studies in Croatia, due to its common presence in the population. However, further multiple investigations from around the world, as numerous as possible, are needed to confirm or deteriorate these preliminary results.

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