scholarly journals Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 907
Author(s):  
Pedro J. Puentes-Rozo ◽  
Johan E. Acosta-López ◽  
Martha L. Cervantes-Henríquez ◽  
Martha L. Martínez-Banfi ◽  
Elsy Mejia-Segura ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Nuclear Families ◽  
Caribbean Community ◽  
Hyperactivity Disorder ◽  
Potential Association ◽  
Family Based ◽  
Genetic Stratification

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

2018 ◽  
Vol 53 (2) ◽  
pp. 217-227 ◽  
Author(s):  
Diego Girotto Bussaneli ◽  
Manuel Restrepo ◽  
Camila Maria Bullio Fragelli ◽  
Lourdes Santos-Pinto ◽  
Fabiano Jeremias ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Nuclear Families ◽  
Molar Incisor Hypomineralization ◽  
Inflammatory Stimuli ◽  
Allele Specific ◽  
Family Based ◽  
And Function

Ameloblasts are sensitive cells whose metabolism and function may be affected by inflammatory stimuli. The aim of this study was to evaluate the possible association between polymorphisms in immune response-related genes and molar-incisor hypomineralization (MIH), and their interaction with polymorphisms in amelogenesis-related genes. DNA samples were obtained from 101 nuclear families that had at least 1 MIH-affected child. Eleven single-nucleotide polymorphisms (SNPs) were investigated in immune response genes using TaqMan® technology allele-specific probes. A transmission disequilibrium test was performed to verify overtransmission of alleles in all MIH families, as well as in families only with mild or severe MIH-affected children. Gene-gene interactions between the immune-related and amelogenesis-related polymorphisms were analyzed by determining whether alleles of those genes were transmitted from heterozygous parents more often in association than individually with MIH-affected children. In severe cases of MIH, significant results were observed for rs10733708 (TGFBR1, OR = 3.5, 95% CI = 1.1–10.6). Statistical evidence for gene-gene interactions between rs6654939 (AMELX) and the SNPs rs2070874 (IL4), rs2275913 (IL17A), rs1800872 (IL10), rs1800587 (IL1A), and rs3771300 (STAT1) was observed. The rs2070874 SNP (IL4) was also significantly overtransmitted from heterozygous parents with the rs7526319 (TUFT1) and the rs2355767 (BMP2) SNPs, suggesting a synergistic effect of the transmission of these alleles with susceptibility to MIH. This family-based study demonstrated an association between variation in TGFBR1 and MIH. Moreover, the polymorphisms in immune response and amelogenesis genes may have an additive effect on the risk of developing MIH.

scholarly journals Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder

2006 ◽  
Vol 189 (4) ◽  
pp. 317-323 ◽  
Author(s):  
Daniel J. Müller ◽  
Vincenzo De Luca ◽  
Tricia Sicard ◽  
Nicole King ◽  
John Strauss ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Rapid Cycling ◽  
Nucleotide Polymorphisms ◽  
Bdnf Gene ◽  
Single Nucleotide ◽  
Nuclear Families ◽  
Family Based ◽  
The Brain

BackgroundWe have previously reported the Val66Met and GT(n) repeat polymorphisms of the brain-derived neurotrophic factor (BDNF) gene to be associated with bipolar disorder. However, these findings have not been replicated consistently.AimsTo dissect the association of the BDNF gene with bipolar disorder by examining additional markers at the DNA level and by testing the illness categories of bipolar disorder I and II and rapid cycling.MethodWe performed a family-based association study and haplotype analyses with 312 nuclear families using four single nucleotide polymorphisms (SNPs) and the Val66Met and GT(n) repeat polymorphisms.ResultsThe SNPs hCVI1592756 and rs2049045, the Val66Met and GT(n) were significantly associated with bipolar disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and 0.008 respectively). The effect at these markers was mainly driven by the rapid-cycling patients.ConclusionsWithin bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according to DSM–IV. Incorporating this clinical sub-phenotyping into other studies of the BDNF gene may help to resolve some of the inconsistencies reported thus far concerning BDNF and bipolar disorder.

scholarly journals Detecting Genetic Associations betweenATG5and Lupus Nephritis bytrans-eQTL

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yue-miao Zhang ◽  
Fa-juan Cheng ◽  
Xu-jie Zhou ◽  
Yuan-yuan Qi ◽  
Ping Hou ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Information ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Genome Wide ◽  
Custom Made ◽  
Regulatory Effects

Objectives. Numerous loci were identified to perturb gene expression intrans. As elevatedATG5expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated withATG5expression in a Chinese population with lupus nephritis (LN).Methods. The online expression quantitative trait loci database was searched fortrans-expression single nucleotide polymorphisms (trans-eSNPs) ofATG5. Taggingtrans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed.Results. Fourtrans-eSNPs were observed to be associated with susceptibility to LN (P< 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven othertrans-eSNPs showed marginal significant associations (0.05 <P< 0.1). Correlations between thetrans-eSNPs andATG5expression and different expression levels ofATG5in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes oftrans-eSNPs and severity or outcome of the patients.Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.

scholarly journals Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations

2019 ◽  
Vol 33 ◽  
pp. 205873841985857 ◽  
Author(s):  
Francesco Carinci ◽  
Annalisa Palmieri ◽  
Luca Scapoli ◽  
Francesca Cura ◽  
Francesco Borelli ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Folic Acid Supplementation ◽  
Nucleotide Polymorphisms ◽  
Orofacial Clefts ◽  
Single Nucleotide ◽  
Candidate Gene Association ◽  
Folate Pathway ◽  
Family Based ◽  
Gene Association Study

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.

scholarly journals Candidate single nucleotide polymorphisms of irritable bowel syndrome: a systemic review and meta-analysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiwei Zhu ◽  
Ben Wang ◽  
Qiong Jia ◽  
Liping Duan
Keyword(s):  
Irritable Bowel Syndrome ◽  
Single Nucleotide Polymorphisms ◽  
Meta Analysis ◽  
Systemic Review ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Increased Risk ◽  
Rome Iii ◽  
Irritable Bowel

Abstract Background Genetic factors increase the risk of irritable bowel syndrome (IBS). Analysis of single nucleotide polymorphisms (SNPs) has been used in IBS patients, but the findings are inconsistent. The goal of this review was to synthesize all the published SNPs studies of IBS through meta-analysis to objectively evaluate the relevance of SNPs to IBS risks. Methods IBS - related polymorphisms studies from 2000 to 2018 were searched. Pooled odds ratios with a 95% confidence interval for each SNP were evaluated through five genetic models. Ethnicity, ROME criteria and IBS subtypes were defined for subgroup analyze. Results Ten relevant genes were evaluated. SNPs rs4263839 and rs6478108 of TNFSF15 associated with an increased risk of IBS; IL6 rs1800795 increased the risk for Caucasian IBS patients which diagnosed by Rome III criteria; and IL23R rs11465804 increased the risk for IBS-C patients. IL10 rs1800896 GG genotype associated with a decreased risk of IBS. No evidence supported the association of GNβ3 rs5443, TNFα rs1800629, and IL10 rs1800871 to IBS in this study. Conclusions This meta-analysis presents an in-depth overview for IBS SNPs analysis. It was confirmed that polymorphisms of TNFSF15 associated with increased IBS risk, while IL10 rs1800896 associated with decreased IBS risk. It might offer some insights into polymorphisms of inflammation factors which might affect IBS susceptibility. Moreover, the analysis also emphasizes the importance of diagnostic criteria and phenotype homogeneity in IBS genetic studies.

Association analyses of depression and genes in the hypothalamus–pituitary–adrenal axis

2016 ◽  
Vol 29 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Henrietta Nørmølle Buttenschøn ◽  
Jesper Krogh ◽  
Marit Nyholm Nielsen ◽  
Linda Kaerlev ◽  
Merete Nordentoft ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Genetic Variants ◽  
Stressful Life Events ◽  
Potential Candidate ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Association Analyses ◽  
Potential Candidate Gene ◽  
Potential Association

ObjectiveDysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE).MethodsIn total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated.ResultsAfter quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified.ConclusionThe results indicate that ACE could be a potential candidate gene for depression.

scholarly journals Genetic approaches to studying virulence and pathogenesis in Toxoplasma gondii

2002 ◽  
Vol 357 (1417) ◽  
pp. 81-88 ◽  
Author(s):  
L. David Sibley ◽  
Dana G. Mordue ◽  
Chunlei Su ◽  
Paul M. Robben ◽  
Dan K. Howe
Keyword(s):  
Toxoplasma Gondii ◽  
Linkage Mapping ◽  
Protozoan Parasite ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Microarray Studies ◽  
Expressed Sequence ◽  
Surprising Finding ◽  
Host Genes

Toxoplasma gondii is a common protozoan parasite that causes disease in immunocompromised humans. Equipped with a wide array of experimental tools, T. gondii has rapidly developed as a model parasite for genetic studies. The population structure of T. gondii is highly clonal, consisting of three distinct lineages that differ dramatically in virulence. Acute virulence is probably mediated by the genetic differences that distinguish strain types. We have utilized a combination of genetic approaches to investigate the acute virulence of toxoplasmosis using the mouse model. These studies reveal the surprising finding that pathogenicity is due to the over–stimulation of normally protective immune responses. Classical genetic linkage mapping studies indicate that genes that mediate acute virulence are linked to chromosome VII in the parasite. To increase the resolution of genetic mapping studies, single–nucleotide polymorphisms are being developed based on an extensive database of expressed sequence tags (ESTs) from T. gondii . Separately, DNA microarray studies are being used to examine the expression of parasite and host genes during infection. Collectively, these approaches should improve current understanding of virulence and pathogenicity in toxoplasmosis.

scholarly journals Screening of single nucleotide polymorphisms among fuchs’ endothelial corneal dystrophy subjects in Malaysia

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ker Hsin Ng ◽  
Visvaraja Subrayan ◽  
Vasudevan Ramachandran ◽  
Fazliana Ismail
Keyword(s):  
Tertiary Care ◽  
Corneal Dystrophy ◽  
Nucleotide Polymorphisms ◽  
Older Individuals ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Novel Variant ◽  
Different Populations ◽  
Larger Sample ◽  
Control Study

Abstract Background The pathophysiology underlying Fuchs' Endothelial Corneal Dystrophy (FECD), especially in older individuals, remains unclear, with a genetic predisposition being reported as the single best predictor of the disease. Genetic studies have shown that several genes in various loci such as COL8A2, SLC4A11, TCF8/ZEB1 and TCF4 are associated with FECD in different populations and ethnicities. A case–control study was conducted to determine the association between genetic variants and FECD in a tertiary care setting in Malaysia. A total number of 12 patients with clinically diagnosed FECD and 12 age, gender and race matched control subjects were recruited. Extracted genomic DNA were genotyped using Infinium Global Screening Array (GSA)-24 version 1.0 BeadChip with iScan high-throughput system. Illumina GenomeStudio 2.0 Data Analysis and PLINK version 1.9 software were used to perform association tests and determine the distribution of obtained variants among the cases and controls. Results A significant novel genetic variant, rs11626651, a variant of the LOC105370676 gene or known as the LINC02320 gene, located at chromosome 14, has been identified as a suggestive association with FECD (p < 5 × 10−6). Further analysis in this study suggested that candidate genes such as COL8A2, ZEB1/TCF8, TCF4 and SLC4A11 had no significant associations with FECD. Conclusions The discovery of a novel variant may influence the underlying pathogenic basis of FECD in Malaysia. The current study is the first genetic study on FECD to use Infinium GSA. It is the first comprehensive report in Malaysia to provide genetic information of potential relevance to FECD, which may pave the way for new therapeutic strategies in the future. A detailed analysis with a larger sample size is recommended for further evaluation.

Association of PPARG Gene Polymorphisms Pro12Ala with Type 2 Diabetes Mellitus: A Meta-analysis

2019 ◽  
Vol 15 (4) ◽  
pp. 277-283 ◽  
Author(s):  
Junyan Li ◽  
Xiaohong Niu ◽  
JianBo Li ◽  
Qingzhong Wang
Keyword(s):  
Publication Bias ◽  
Chinese Population ◽  
Meta Analysis ◽  
Genetic Data ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Combined Analysis ◽  
Pparg Gene

Background:Previous studies suggested that the single nucleotide polymorphisms of Pro12Ala located within the PPARG gene were significantly associated with the T2DM. Recently, the genetic studies on Pro12Ala were conducted in the different ethnic groups and the results of each study were shown to be inconsistent. Moreover, the systematic review has not been updated since 2000.Objective:To further validate the risk of Pro12Ala for T2DM disease based on the genetic data.Methods:The genetic studies on the Pro12Ala in the T2DM were searched in the PubMed and PMC database from January 2000 to October 2017. The meta-analysis was conducted with the CMA software.Results:The meta-analysis collected 14 studies including 20702 cases and 36227 controls. The combined analysis of all studies found that Pro12Ala was shown to be significantly associated with T2DM and the Ala allele played the increasing risks for the disease. Nevertheless, publication bias was detected in the combined analysis. The subgroup analysis indicated that Pro12Ala was found to be significant in the Caucasian and Chinese population. There was no heterogeneity and publication bias in these two groups.Conclusion:The meta-analysis confirmed the evidence that the Pro12Ala was the susceptible variant for the decreasing risks for the T2DM

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