Potential Role Of Genetic Factors Research Articles

The role of NOS3-rs1799983 and NOS3- rs2070744 SNP in occurrence of avascular necrosis as a post COVID-19 complication

Avascular necrosis (AVN) is a debilitating condition characterized by bone tissue death due to inadequate blood supply, leading to joint dysfunction and collapse. This study investigates the potential association between AVN and COVID-19, focusing on genetic factors such as NOS3 polymorphisms. A total of 180 individuals were included, comprising 120 COVID-19 patients and 60 healthy controls. Clinical, haematological, biochemical, and genetic parameters were assessed. Results revealed significant differences in respiratory and heart rates, haematological counts, and biochemical markers between AVN and control groups. Genetic analysis showed a higher prevalence of the TG genotype and G allele in NOS3 rs1799983 polymorphism among AVN patients. Additionally, NOS3 rs2070744 polymorphism correlated with various clinical parameters, including blood pressure, heart rate, and haematological indices. This study highlights the potential role of genetic factors in predisposing individuals to AVN following COVID-19 infection.

Association of TaqI (rs731236) Polymorphism of Vitamin D Receptor Gene with Lumbar Degenerative Disc Disease

Lumbar degenerative disc disease (LDDD) significantly contributes to low back pain, with a complicated etiology involving genetic and environmental facts. The aim of study was to investigate the association between the TaqI (rs731236) polymorphism of the vitamin D receptor (VDR) gene with LDDD. In total, 248 patients with symptomatic LDDD and 146 control subjects were examined. The evaluation of clinical features of patients with LDDD comprised radiodiagnostic magnetic resonance imaging, neurologic examinations, pain scores including the visual analog scale (VAS), and disability investigation with Oswestry Disability Index (ODI). Genotyping of the VDR gene polymorphism was conducted using polymerase chain reaction-based methods. Individuals of the LDDD group who were VDR TaqI AA genotype carriers were significantly greater than the other group (P= 0.014), whereas those with GG genotype were significantly lower (P= 0.028) in the patient group. In addition, VAS and ODI scores were significantly lower in the GG genotype carrier group, whereas AA genotype carriers had the greatest scores (P= 0.004). Carrying the G allele decreased the risk of LDDD 1.7 times (P= 0.014) and carrying the A allele enhanced the risk 1.8 times (P= 0.028). Moreover, G-allele carriers had significantly lower VAS (P= 0.002) and ODI scores (P < 0.0001). VDR TaqI (rs731236) GG genotype and G allele have protective potential, whereas the AA genotype and A allele are risk factors for LDDD. The findings reveal a statistically significant association of the TaqI (rs731236) polymorphism of VDR gene polymorphism with LDDD. This result highlights the potential role of genetic factors in developing LDDD and suggests avenues for future research in genetic screening and personalized treatment strategies.

FTO and MC4R polymorphisms, and selected pre-, peri- and postnatal factors as determinants of body mass index and fatness in children: a thorough analysis of the associations

BackgroundOverweight and obesity among children have become significant global health concerns. Previous studies have highlighted the potential role of genetic factors, particularly polymorphisms in the FTO and MC4R genes, as well as environmental factors in the development of childhood obesity. This study aimed to investigate the relationships between genetic, socioeconomic and perinatal factors, adverse childhood events (ACEs), and lifestyle, and their impact on overweight, obesity and body composition parameters in children. Additionally, we explored potential interactions between genetic factors and ACEs.MethodsFour hundred fifty-six children aged 6–12 years participated in our study. Information on the socioeconomic status, perinatal factors, ACEs and lifestyle of the children was collected with a questionnaire completed by their parents/guardians. We examined the children’s body weight and conducted an electrical bioimpedance analysis. Overweight and obesity were diagnosed based on the International Obesity Task Force and McCarthy criteria. We genotyped two selected polymorphisms in the FTO and MC4R genes using the TaqMan SNP allelic discrimination method.ResultsHigher BMI (Body Mass Index) z scores were related to higher paternal BMI and lower maternal age at the child’s birth. Higher FMI (Fat Mass Index) z scores were associated with higher paternal BMI, increased gestational weight, lower maternal education and the presence of the FTO risk allele. Higher FatM (fat mass in kg) z scores were linked to lower maternal education, lower maternal age at the child’s birth, higher maternal body weight gain, paternal BMI and the presence of the FTO risk allele. Moreover, interaction effects were observed on BMI z scores between ACE and FTO AA, and on FMI z scores and FatM z scored between ACE and MC4R CC.ConclusionsThe contribution of environmental factors is more strongly related to changes in body composition than genetic ones. Additionally, the presence of the risk allele combined with unfavourable environmental factors like ACEs leads to visible interaction effects, resulting in increased BMI z scores and FMI z scores in children.

Analysis of the Relationship Between MAOA and CDH-13 Genes and Crime

When scholars investigate criminal behaviour, they observe the existence of several criminal organizations characterized by a continuous involvement in illegal activities over successive generations. There is a potential hereditary transmission of criminal conduct. The topic of heredity invariably encompasses the issue of chromosomes and genes, as these elements are essential to the process of heredity. Currently, there is a lack of empirical evidence supporting the notion of criminal genes, and the consensus among scholars in the field of criminal psychology is that criminal behaviour is a multifaceted outcome influenced by physiological, social, and psychological factors. In contemporary times, within the framework of the expeditious advancement of science and technology, there has been a corresponding escalation in the incidence of criminal activities. Researchers have extensively investigated potential connections or shared characteristics among individuals involved in criminal activities across numerous situations. Scientists have directed their attention on genes, seeing them as the fundamental basis of emerging biotechnologies. This research employs a literature review and analysis method to provide a succinct description of the association between the MAOA (Monoamine oxidase A) and CDH-13 (Cadherin-13) genes and criminal behaviour. Furthermore, it examines specific instances to investigate the potential role of genetic factors in contributing to criminal tendencies.

The effects of early rearing experiences on mutual eye gaze among captive olive baboons (Papio anubis).

Among human and nonhuman primates, mutual eye gaze (MEG) and gaze following are believed to be important for social cognition and communicative signaling. The goals of this study were to examine how early rearing experiences contribute to individual variation in MEG and to examine the potential role of genetic factors underlying this variation. Subjects included 93 female and 23 male baboons (Papio anubis) ranging from 3 to 20 years of age. Within the sample, there were 55 mother-reared (MR) and 61 nursery-reared (NR) baboons. MEG was assessed in four 60-s test sessions. For each session, the duration, frequency, and bout length were recorded. Mean values were then calculated for each individual from the four sessions. A multivariate analysis of covariance revealed an overall significant main effect for rearing. Subsequent univariate analyses revealed significant rearing effects on mean bout length, but not mean duration or meanfrequency, with MR baboons having longer bout lengths compared to NR baboons. Furthermore, mean bout length was found to be significantly heritable. These results indicate that rearing experiences, and to a small extent, genetic factors, affect patternsof mutual eye gaze - in particular, bout length. These results differ from previous findings in MR and NR chimpanzees, further suggesting that rearing may impact MEG in a species-specific manner that reflects the function of gaze in different primate species.

Acute mesenteric ischemia secondary to superior mesenteric vein thrombosis in a patient with liver cirrhosis: A case report.

Acute mesenteric ischemia due to superior mesenteric vein (SMV) thrombosis is a rare yet potentially life-threatening emergency. Our case report explores this condition in the context of a patient with liver cirrhosis due to Wilson disease. We specifically highlight the complex derangement of the coagulative balance in liver cirrhosis. A 34-year-old female with Wilson disease-related cirrhosis presented with intractable abdominal pain, nausea, and vomiting that showed no response to antispasmodic medication. A contrast-enhanced abdominal computed tomography scan and Doppler ultrasound confirmed an intraluminal filling defect in the SMV, leading to the diagnosis of SMV thrombosis. Prompt anticoagulation, intravenous fluids, and an antibiotic were initiated. Surgical consultation recommended conservative therapy with close monitoring. Over the following 2 days, the patient's condition improved considerably, with almost complete resolution of her symptoms. Genetic testing identified a 4G/4G homozygous genotype of the plasminogen activator inhibitor 1 gene, associated with a higher risk of thrombosis in the vessels of internal organs. After 2 months of sustained anticoagulant therapy, a follow-up contrast-enhanced computed tomography scan revealed near-complete recanalization of the SMV, and the patient remained symptom-free. This case underscores the importance of early detection and treatment of acute mesenteric ischemia in patients with liver cirrhosis, as well as the potential role of genetic factors in thrombosis.

Multimodal Imaging Reveals Bilateral Idiopathic Multiple Retinal Pigment Epithelial Detachments: A Case Report

Background: Retinal pigment epithelial detachment (RPED) is a nonspecific finding that is common in several ocular diseases; however, cases of bilateral idiopathic multiple RPEDs are rare. Less than 50 cases have been reported to date. Bilateral multiple RPEDs are usually idiopathic and benign in nature but can infrequently be associated with various ocular and systemic diseases, including central serous chorioretinopathy (CSC). The potential role of genetic factors in this condition remains elusive. We present a case where multimodal imaging assisted in revealing the diagnosis as well as discuss the potential implications of some of the genetic findings for this patient. Case report: A 30-year-old male presented with a chief complaint of mild, bilateral central blur of one-year duration. Health history was positive for type 2 diabetes mellitus. Conclusion: Multimodal ophthalmic imaging is useful in ruling out various differential diagnoses in posterior segment care, as well as monitoring for progressive changes such as sensory retinal detachment and choroidal neovascularization. Bilateral idiopathic multiple RPED is a rare condition that may represent an atypical form of CSC. There is currently no preferred treatment, besides observation, as visual prognosis is typically good.

Genetic predispositions to psychiatric disorders and the risk of COVID-19

BackgroundWhether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown.MethodsOur analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population (“base dataset”). For the other half (“target dataset”), the polygenic risk score (PRS) was calculated as a proxy of individuals’ genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered “severe cases.” The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics.ResultsA total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02–1.13) and 1.06 (95% CI 1.01–1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics.ConclusionsOur findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.

Genome-Wide Heritability Estimates for Family Life Course Complexity.

Sequence analysis is an established method used to study the complexity of family life courses. Although individual and societal characteristics have been linked with the complexity of family trajectories, social scientists have neglected the potential role of genetic factors in explaining variation in family transitions and events across the life course. We estimate the genetic contribution to sequence complexity and a wide range of family demographic behaviors using genomic relatedness-based, restricted maximum likelihood models with data from the U.S. Health and Retirement Study. This innovative methodological approach allows us to provide the first estimates of the heritability of composite life course outcomes-that is, sequence complexity. We demonstrate that a number of family demographic indicators (e.g., the age at first birth and first marriage) are heritable and provide evidence that composite metrics can be influenced by genetic factors. For example, our results show that 11% of the total variation in the complexity of differentiated family sequences is attributable to genetic influences. Moreover, we test whether this genetic contribution varies by social environment as indexed by birth cohort over a period of rapid changes in family norms during the twentieth century. Interestingly, we find evidence that the complexity of fertility and differentiated family trajectories decreased across cohorts, but we find no evidence that the heritability of the complexity of partnership trajectories changed across cohorts. Therefore, our results do not substantiate claims that lower normative constraints on family demographic behavior increase the role of genes.

WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides.

Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases.

The role of genetic factors in carpal tunnel syndrome etiology: A review.

The direct causes of idiopathic carpal tunnel syndrome (CTS) still remain obscure. It has been suggested that the pathology of tendons and other connective tissue structures within the carpal tunnel may be involved in its etiology. The objective of this study was to review the literature about the potential role of genetic factors in the etiology of CTS. Three different mechanisms are suspected to be involved in genetic predisposition to CTS: collagen synthesis, collagen degradation and protection against oxidative stress effect in connective tissue. Several gene groups are involved in the regulation and modulation of these mechanisms, and the research reviewed in this study showed their possible effect on the development of CTS. Variants within the COL1A1, COL5A1 and COL11A1 genes - encoding the synthesis of minor collagen subtypes - may potentially be involved, as they alter the mechanical properties of tendons and other connective tissue structures within the carpal tunnel. The collagen within connective tissue structures is also remodeled by matrix metalloproteinases (MMPs), so variants of these genes have also been investigated for their possible role in the risk of CTS development. Next, the variants of genes encoding glutathione S-transferase (GST) synthesis were found to be involved in the etiology of CTS. The findings from the abovementioned studies provide reliable information on the potential role of genetic risk factors in the development of CTS.

Quantitative trait loci analysis reveals candidate genes implicated in regulating functional deficit and CNS vascular permeability in CD8 T cell-initiated blood–brain barrier disruption

BackgroundBlood–brain barrier (BBB) disruption is an integral feature of numerous neurological disorders. However, there is a relative lack of knowledge regarding the underlying molecular mechanisms of immune-mediated BBB disruption. We have previously shown that CD8 T cells and perforin play critical roles in initiating altered permeability of the BBB in the peptide-induced fatal syndrome (PIFS) model developed by our laboratory. Additionally, despite having indistinguishable CD8 T cell responses, C57BL/6J (B6) mice are highly susceptible to PIFS, exhibiting functional motor deficits, increased astrocyte activation, and severe CNS vascular permeability, while 129S1/SvImJ (129S1) mice remain resistant. Therefore, to investigate the potential role of genetic factors, we performed a comprehensive genetic analysis of (B6 x 129S1) F2 progeny to define quantitative trait loci (QTL) linked to the phenotypic characteristics stated above that mediate CD8 T cell-initiated BBB disruption.ResultsUsing single nucleotide polymorphism (SNP) markers and a 95% confidence interval, we identified one QTL (PIFS1) on chromosome 12 linked to deficits in motor function (SNP markers rs6292954, rs13481303, rs3655057, and rs13481324, LOD score = 3.3). In addition we identified a second QTL (PIFS2) on chromosome 17 linked to changes in CNS vascular permeability (SNP markers rs6196216 and rs3672065, LOD score = 3.7).ConclusionsThe QTL critical intervals discovered have allowed for compilation of a list of candidate genes implicated in regulating functional deficit and CNS vascular permeability. These genes encode for factors that may be potential targets for therapeutic approaches to treat disorders characterized by CD8 T cell-mediated BBB disruption.

Cancer prevention: major initiatives and looking into the future

Cancer is one of the major causes of death in countries across the world. However, at least half of cancers could be prevented. This article reviews the relationship between cancer incidence and the major risk factors: tobacco use, exposure to infections, nutrition, obesity and physical activity. Several major current cancer prevention initiatives are presented, including the effort for global tobacco control, vaccination programs for human papilloma virus, chemoprevention, and cohort studies to identify and elucidate cancer causes. Two concerns that cross the cancer prevention research spectrum are the importance of social determinants of health, and the potential role of genetic factors in explaining cancer incidence and guiding intervention development. In the future, optimism is warranted regarding cancer prevention. If currently known criteria are applied and extended, significant reductions in cancer rates are possible.

Genetic bases of urinary albumin excretion and related traits in hypertension

Epidemiological as well as animal studies have recognized the potential role of genetic factors in the development of microalbuminuria and related traits (renal insufficiency, end-stage renal disease and nephroangiosclerosis) in hypertension. To unravel genetic variants of susceptibility, candidate gene, linkage and genome wide scan analysis has been used. In spite of the great efforts that have been made in the field, sound knowledge about the major genetic variants causing the susceptibility to develop renal damage in hypertension is scarce, since many associations were not replicated or only showed association in a certain subgroup of patients. Looking initially at genes of the most important physiological pathways of blood pressure regulation, linkage and genome wide scan have also detected genes of the lipid metabolism and protein components of the glomerular structures as potential candidate genes. Well designed large-scale genome-wide analysis and replication studies with large cohorts can help in the future to clarify the genetic bases of renal damage in hypertension. Combined strategies can contribute toward a better understanding of the genetic basis of urinary albumin excretion and renal damage in hypertension

Update on Mechanisms of Ultrafiltration Failure

Ultrafiltration failure (UFF) continues to be a major complication of peritoneal dialysis (PD), particularly long-term PD. Continuous exposure to bioincompatible PD solutions causes inflammation of the peritoneal membrane, which progressively undergoes fibrosis and angiogenesis and, ultimately, UFF. There is emerging evidence that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (MCs) may play an important role in the failure of peritoneal membrane function. Submesothelial myofibroblasts originating from MCs through EMT and from activated resident fibroblasts participate in inflammatory responses, extracellular matrix accumulation, and angiogenesis. High glucose and glucose degradation products from PD solutions are responsible for production of transforming growth factor beta (TGFbeta) and vascular endothelial growth factor (VEGF) by MCs, which induce EMT. Leptin and receptor for advanced glycation end-products (AGEs) augment myofibroblastic conversion through the TGFbeta signaling system. A reduction in osmotic conductance in addition to increased solute transport causes UFF. This situation may be caused by loss of aquaporin (AQP) function and formation of the submesothelial fibrotic layer. During PD, AQP1 plays an essential role in water permeability and ultrafiltration (UF), modulating processes such as endothelial permeability and angiogenesis. During a hypertonic dwell, AQP1 mediates 50% of UF. Insufficient AQP1 function may be causative for inadequate UFF. A significant amount of evidence from animal studies now exists to show that mast cells communicate with fibroblasts and are implicated in fibrogenesis, angiogenesis, and UFF. However, it is not confirmed in human studies that mast cells contribute to the fibrosis seen in the peritoneum of PD patients. The patterns of UFF in PD patients depend on duration of treatment. Inherently high small-solute transport status is associated with hypoalbuminemia and a greater comorbidity index. However, most of the variability in peritoneal transport remains unexplained, pointing to the potential role of genetic factors. Gene polymorphisms associated with peritoneal membrane transport have been identified. Recent studies have shown that VEGF, interleukin-6, endothelial NO synthase, AGE receptor, and RAS gene polymorphisms are associated with transport properties in PD patients. Current insights into the mechanisms of UFF will provide rationales for new therapeutic strategies.

Consanguinity and the risk of hyperemesis gravidarum in Norway

Hyperemesis gravidarum (HG) is a condition that occurs in the first half of pregnancy, and is manifested by severe vomiting, electrolyte disturbances and weight loss. Previous studies have suggested the potential role of genetic factors in the aetiology of HG. We hypothesise that consanguineous relations between parents increase the risk of HG due to the increased risk of homozygosity in HG-associated alleles in a fetus. Moreover, we examine whether ethnic variations in the occurrence of HG can be attributed to consanguinity. All Norwegian, Pakistani and Turkish primiparous women with singleton pregnancies registered in the Norwegian Medical Birth Registry (MBRN) from 1967 to 2005 comprised the sample. Data on HG and potential confounders were obtained from MBRN. Multiple logistic regression was used to study associations between the degrees of relationship between women and their partners and the prevalence of HG. Crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated. The prevalence of HG was 0.9, 2.2 and 1.9% in Norwegian, Pakistani and Turkish women, respectively. Norwegian (OR =0.93; 95% CI: 0.42-2.09), Pakistani (OR =1.08; 95% CI: 0.68-1.74) and Turkish (OR =1.08; 95% CI: 0.44-2.67) women related to their partners as first cousins had similar risks of HG as non-related women after adjustment for potential confounders. Consanguinity was not associated with HG in this study. The differences in the occurrence of HG between Norwegian, Pakistani and Turkish women are not attributed to consanguinity.

Applied Principles of Neurogastroenterology: Physiology/Motility Sensation

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.

Bio‐social determinants of fertility

This paper reviews several studies that investigated the potential role of genetic factors in determining fertility outcomes. Our review demonstrates convincingly that fertility contains genetic variance; that is, differences between humans in their genetic make-up affects their fertility outcomes and fertility-related behaviours. This finding is robust using both heritabilities and coefficients of genetic variation, and using both direct measures of fertility outcomes and also fertility precursors like fecundity, marriage, fertility expectations and attempts to get pregnant (proception). Moreover, genetic variance can change over short periods of time or across educational levels, specifically for females, and the relevance of genetic variance seems to increase during times of increasing reproductive choice.

Olfactory Function in Monozygotic Twins Discordant for Schizophrenia

Abnormalities of olfactory identification ability have been proposed as a marker of cerebral dysfunction in schizophrenia. The authors studied the potential role of genetic factors in olfactory dysfunction by assessing monozygotic twins discordant for schizophrenia and matched comparison subjects. The subjects were 12 pairs of monozygotic twins discordant for schizophrenia and 12 healthy subjects matched for sex and age. Each subject completed the University of Pennsylvania Smell Identification Test. The combined twin group scored significantly lower on smell identification than did the comparison group. The affected and unaffected twin groups did not differ from each other. Genetic factors may contribute to cerebral dysfunction as assessed by olfactory identification ability.

Family history of seizures in posttraumatic and alcohol-associated seizure disorders.

The potential role of genetic factors in the etiology of posttraumatic and alcohol-associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first-degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcohol-associated seizures had a rate ratio of 2.45 [95% confidence interval (CI) 1.41-4.25], whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64-2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92-3.20 CI). Among probands with alcohol-associated seizures, the rate ratio of 2.05 for patients with alcohol-related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcohol-related seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures.