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International Journal of Molecular... Jun 2024Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to...
Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.
Topics: Humans; Filaggrin Proteins; Intermediate Filament Proteins; Polymorphism, Single Nucleotide; Female; Male; Asian People; Adult; Middle Aged; Exome Sequencing; Genetic Predisposition to Disease; Psoriasis; Aged; Interferon-gamma; Autoantibodies; Skin
PubMed: 38928170
DOI: 10.3390/ijms25126466 -
International Journal of Molecular... Jun 2024It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral...
It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait ( < 0.0001) and neuroticism ( < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A ( < 0.0001) and G/G ( = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A ( < 0.0001) and G/G ( < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Female; Alcoholism; Adult; Polymorphism, Single Nucleotide; Personality; Middle Aged; Anxiety; Genetic Predisposition to Disease; Genotype; Neuroticism; Case-Control Studies
PubMed: 38928154
DOI: 10.3390/ijms25126448 -
International Journal of Molecular... Jun 2024The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a... (Review)
Review
The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.
Topics: Humans; Diabetic Neuropathies; Genetic Predisposition to Disease; Genetic Variation; Animals
PubMed: 38928135
DOI: 10.3390/ijms25126429 -
International Journal of Molecular... Jun 2024Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic...
Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic β-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). -MODY 2 was the most frequently detected variant, but rare forms of -MODY 13, specifically, -MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype-phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context.
Topics: Humans; Diabetes Mellitus, Type 2; Genetic Testing; Male; Female; Genetic Counseling; Adult; Precision Medicine; High-Throughput Nucleotide Sequencing; Adolescent; Potassium Channels, Inwardly Rectifying; Young Adult; Child; Hepatocyte Nuclear Factor 4; Exome Sequencing; Genetic Predisposition to Disease; Mutation
PubMed: 38928025
DOI: 10.3390/ijms25126318 -
International Journal of Molecular... Jun 2024Sickle cell disease (SCD) clinically manifests itself with a myriad of complications. Stroke, both ischemic and hemorrhagic, as well as silent white matter changes,... (Review)
Review
Sickle cell disease (SCD) clinically manifests itself with a myriad of complications. Stroke, both ischemic and hemorrhagic, as well as silent white matter changes, occurs at a relatively high prevalence. Understanding why and in whom stroke is most likely to occur is critical to the effective prevention and treatment of individuals with SCD. Genetic studies, including genome- and exome-wide association studies (GWAS and EWAS), have found several key modifiers associated with increased stroke/stroke risk in SCD via mechanisms including Hemoglobin F (HbF) modulation, inflammation, cellular adhesion, endothelial disruption, and hemolysis. We present a review on the modifiers that have most clearly demonstrated an association to date. More studies are needed to validate other potential polymorphisms and identify new ones. Incorporating gene-focused screenings in clinical care could provide avenues for more targeted, more effective, and less toxic prevention of stroke in this population. The data from this review will be used to inform the initial GWAS performed by the International Hemoglobinopathy Research Network (INHERENT) consortium.
Topics: Humans; Anemia, Sickle Cell; Stroke; Genome-Wide Association Study; Genetic Predisposition to Disease; Genes, Modifier; Fetal Hemoglobin
PubMed: 38928024
DOI: 10.3390/ijms25126317 -
Genes Jun 2024Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a...
Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: , , and . Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case-control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 ( = 0.04) and rs16903247 ( = 0.05) genotypes within the gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings-rs3776578 ( = 0.0041) and rs16903247 ( = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of . The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of .
Topics: Humans; Polymorphism, Single Nucleotide; Migraine Disorders; Female; Male; Excitatory Amino Acid Transporter 1; Adult; Case-Control Studies; Genetic Predisposition to Disease; Middle Aged; Genetic Association Studies
PubMed: 38927733
DOI: 10.3390/genes15060797 -
Genes Jun 2024Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of...
BACKGROUND
Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single nucleotide polymorphisms (SNPs) in dopaminergic receptor (DR) genes have been extensively studied, their role in MS progression remains unexplored. Therefore, the aim of this explorative study is to investigate the potential association between functional SNPs in DR genes and MS progression.
METHODS
Caucasian patients with relapsing-remitting (RR) MS were enrolled, and disease progression assessed by the Multiple Sclerosis Severity Score (MSSS).
RESULTS
Out of the 59 RRMS patients enrolled, those with the G/G genotype for rs6280 and rs1800828 SNPs in DRD3 showed significantly higher MSSSs compared to those with ancestral and heterozygous genotypes.
CONCLUSIONS
If confirmed in a larger prospective study, the reported findings could contribute to a better understanding of MS pathophysiological mechanisms, opening the way for the identification of marker(s) for assessing MS progression as well as novel therapeutic strategies. A personalized approach to MS management has the potential to improve the overall well-being of MS patients and alleviate the burden on their caregivers.
Topics: Humans; Multiple Sclerosis, Relapsing-Remitting; Female; Male; Polymorphism, Single Nucleotide; Adult; Receptors, Dopamine D3; Disease Progression; Middle Aged; Genotype; Genetic Predisposition to Disease
PubMed: 38927672
DOI: 10.3390/genes15060736 -
Genes Jun 2024Aquaculture supplies the world food market with a significant amount of valuable protein. Highly productive aquaculture fishes can be derived by utilizing genome-editing... (Review)
Review
Aquaculture supplies the world food market with a significant amount of valuable protein. Highly productive aquaculture fishes can be derived by utilizing genome-editing methods, and the main problem is to choose a target gene to obtain the desirable phenotype. This paper presents a review of the studies of genome editing for genes controlling body development, growth, pigmentation and sex determination in five key aquaculture Salmonidae and Cyprinidae species, such as rainbow trout (), Atlantic salmon (), common carp (), goldfish (), Gibel carp () and the model fish zebrafish (). Among the genes studied, the most applicable for aquaculture are , , and , the knockout of which leads to enhanced muscle growth; , mutants of which do not form bones in myoseptae; , whose lack of function makes fish fast-growing; , , and , affecting the composition of fatty acids in fish meat; , and , mutants of which are sterile; and disease-susceptibility genes , , , and . Schemes for obtaining common carp populations consisting of only large females are promising for use in aquaculture. The immobilized and uncolored zebrafish line is of interest for laboratory use.
Topics: Animals; Gene Editing; Aquaculture; Phenotype; Cyprinidae
PubMed: 38927661
DOI: 10.3390/genes15060726 -
Genes Jun 2024The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population...
The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.
Topics: Humans; Adenosine Triphosphatases; Aortic Dissection; Asian People; Genetic Predisposition to Disease; Intracranial Aneurysm; Moyamoya Disease; Polymorphism, Single Nucleotide; Ubiquitin-Protein Ligases
PubMed: 38927660
DOI: 10.3390/genes15060725 -
Genes May 2024Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes...
Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the gene, rs429358 and rs7412 for the gene and rs1801157 [-3'G(801)A] for gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the Q192R is likely to play a role as a risk factor for retinal vein occlusion.
Topics: Humans; Aryldialkylphosphatase; Retinal Vein Occlusion; Male; Female; Chemokine CXCL12; Case-Control Studies; Middle Aged; Polymorphism, Single Nucleotide; Aged; Apolipoproteins E; Genetic Predisposition to Disease; Risk Factors; Greece; Haplotypes
PubMed: 38927649
DOI: 10.3390/genes15060712