PHACTR1 and APOC1 genetic variants are associated with multi-vessel coronary artery disease.

BACKGROUND: Severe coronary artery disease (CAD) represents an advanced arterial narrowing, often associated with critical complications like myocardial infarction and angina. This study aimed to comprehensively investigate determinants of severe and multi-vessel CAD manifestations. METHODS: One thousand nine hundred patients with severe and multivessel CAD (stenosis > 70%) were recruited along with 1,056 controls without stenosis. Associations using a genotyping panel comprising 159 Single Nucleotide Polymorphisms (SNPs) previously implicated in CAD pathogenesis were examined and these associations were replicated using the UK Biobank cohort (N = 29,970). RESULTS: The investigation identified 14 genetic associations with severe CAD, of which 7 were also associated with multivessel disease. Notably, PHACTR1 SNP (rs9349379*G) showed a higher association with severe and multivessel CAD in individuals aged ≤ 65, indicating a higher risk of early disease onset. Conversely, the APOC1/APOE SNP (rs445925*T) is associated with reduced susceptibility to severe CAD and multivessel disease in individuals aged over 65, indicating a persistent negative association. CONCLUSIONS: Following replication of the associations in the large UK Biobank dataset, it was found that patients carrying the rs9349379*G variant in the PHACTR1 gene are at risk of developing severe or multivessel disease. Conversely, the rs445925*T variant in APOC1/APOE is associated with reduced susceptibility to severe CAD and multivessel disease, highlighting the significance of this genetic variant in these specific CAD presentations. This study contributes to a better understanding of CAD heterogeneity, paving the way for tailored management strategies based on genetic profiles.

Exploring challenges in learning and study skills among first-year medical students: a case study.

BACKGROUND: Despite being high-achieving students, many medical students face academic challenges, particularly during their first year of study. Research indicates that self-regulated learning, involving metacognitive processes and adaptive strategies, can positively influence academic achievement. This study aimed to assess the early learning and study skills of first-year medical students in an international medical school with the goal of developing a learner-centered educational intervention to promote self-regulated learning. METHODS: We conducted a retrospective analysis of the Learning and Study Skills Inventory (LASSI) questionnaire that was administered annually each August to first-year medical students from 2019 to 2022. The distribution of students across different percentile ranges for each selected variable was determined for each year and all years collectively. Students were counted within distinct percentile brackets (50th and below, between 51st and 75th, and above 75th ) for each variable. RESULTS: A total of 147 students completed the LASSI questionnaire over the 4-year time period. Using academic resources was the greatest concern, with 67% of students in the 50th or below percentile, followed by selecting the main idea (56%), motivation (51%), and concentration (50%). Attitude scored highest across all cohorts, scoring between 21.55 ± 0.73 and 26.49 ± 0.34. In comparing mean scores of LASSI variables across all cohorts, attitude, motivation, test-taking strategies, time management, and the use of academic resources differed significantly (p < 0.05). CONCLUSION: LASSI data can provide an early picture of students' support needs. We posit that early identification of student learning and study skills and areas of struggle can inform personalized educational interventions and programs to support first-year medical students.

Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia.

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.

Impact of silver ions and silver nanoparticles on biochemical parameters and antioxidant enzyme modulations in Saccharomyces cerevisiae under co-exposure to static magnetic field: a comparative investigation.

The increase in simultaneous exposure to magnetic fields and other hazardous compounds released from industrial applications poses multiple stress conditions on the ecosystems and public human health. In this work, we investigated the effects of co-exposure to a static magnetic field (SMF) and silver ions (AgNO3) on biochemical parameters and antioxidant enzyme activities in the yeast Saccharomyces cerevisiae. Sub-chronic exposure to AgNO3 (0.5 mM) for 9 h resulted in a significant decrease in antioxidant enzyme activity, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione transferase (GST). The total glutathione (GSH) level increased in yeast cells exposed to Ag. Additionally, a notable elevation in malondialdehyde (MDA) levels and protein carbonyl content was observed in both the AgNP and AgNO3 groups compared to the control group. Interestingly, the SMF alleviated the oxidative stress induced by silver nitrate, normalizing antioxidant enzyme activities by reducing cellular ROS formation, MDA levels, and protein carbonylation (PCO) concentrations.

The impact of forced displacement: trauma, increased levels of inflammation and early presentation of diabetes in women Syrian refugees.

BACKGROUND: Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon. METHODS: Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed. RESULTS: Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35-55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P = 0.036). CONCLUSIONS: Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees.

The Study to Investigate COVID-19 Infection in People Living in Ireland (SCOPI): A seroprevalence study, June to July 2020.

BackgroundRobust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.AimTo conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.MethodsUsing a cross-sectional study design, we selected population samples from individuals aged 12-69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age-sex distribution, and by simple random sampling within age-sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.ResultsParticipation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05-4.53) and 0.58% (95% CI: 0.18-1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13-2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772-85,176) people aged 12-69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0-4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.ConclusionThe majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June-July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.

Bang the gavel: animal experimentation on trial-an interdisciplinary mock trial at the school of health sciences.

Active learning activities offer opportunities for medical students to facilitate the retention of knowledge and develop soft skills. We aimed to create a guide for an interdisciplinary mock trial learning activity within the medical curriculum of the College of Medicine, Anhembi Morumbi University-Laureate International Universities, Sao Paulo, Brazil. We designed an "Animal Experimentation Mock Trial" in which students are coached to search for scientific, legal, and ethical arguments pro and contra animal experimentation in medical research. The mock trial is prepared and staged with student teams to play the 1) presiding judge, 2) the plaintiff's attorney and expert witnesses contra animal research, 3) the defense attorney and expert witnesses pro animal research, and 4) the jury. The plaintiff and defense teams made presentations, and between each presentation the jury put questions to presenters (cross-examination). The jury team gave two evaluation scores after the plaintiff's presentation and then after the defense presentation. The formal feedback for this active learning activity indicated that students expressed satisfaction with the teaching strategies employed in the course. The mock trial with the lesson plan provides a learning mean to exemplify the complex relationship between animal experimentation, medical evidence, ethics, and law/regulations. This mock trial helps medical students to develop their soft skills, such as the ability to collaborate and also to recognize the limits of their own knowledge, important for professional development. The importance of interdisciplinary discussions is demonstrated by increasing the awareness of the multidisciplinary aspect of animal research.

Hematuria in a 3-month-old filly with an internal umbilical abscess and internal iliac artery aneurysm.

A 3-month-old foal with a history of acute hematuria was evaluated. Hydronephrosis and hydroureter were visualized upon renal ultrasonography of the left kidney. Cystoscopy identified a blood clot occluding the left ureter. Computed tomography (CT) revealed a large retroperitoneal abscess at the level of the aortic bifurcation and a left internal iliac aneurysm. Due to the severity of the lesions and the poor prognosis, the filly was euthanized and the clinical findings were confirmed by post-mortem examination. This report emphasizes the value of obtaining a precise diagnosis via CT in order to avoid unviable treatment approaches when confronted with this unusual secondary complication of omphaloarteritis. Key clinical message: Umbilical complications are routinely diagnosed in equine neonatal medicine, and commonly lead to septicemia, physitis, and septic arthritis; severe internal umbilical abscessation, and subsequent vascular and urinary disorders are uncommon sequelae.

Hématurie chez une pouliche de 3 mois avec abcès ombilical interne et anévrisme de l'artère iliaque interne. Un poulain de 3 mois ayant des antécédents d'hématurie aiguë a été évalué. L'hydronéphrose et l'hydro-uretère ont été visualisés par échographie rénale du rein gauche. La cystoscopie a identifié un caillot sanguin obstruant l'uretère gauche. La tomodensitométrie (TDM) a révélé un gros abcès rétropéritonéal au niveau de la bifurcation aortique et un anévrisme iliaque interne gauche. En raison de la gravité des lésions et du mauvais pronostic, la pouliche a été euthanasiée et les résultats cliniques ont été confirmés par un examen post-mortem. Ce rapport souligne l'intérêt d'obtenir un diagnostic précis par TDM afin d'éviter des approches thérapeutiques non-viables face à cette complication secondaire inhabituelle de l'omphalo-artérite.Message clinique clé :Les complications ombilicales sont couramment diagnostiquées en néonatalogie équine et conduisent généralement à une septicémie, une épiphysite et une arthrite septique; un abcès ombilical interne sévère et des troubles vasculaires et urinaires subséquents sont des séquelles peu fréquentes.(Traduit par Dr Serge Messier).

Case Manifestations and Public Health Response for Outbreak of Meningococcal W Disease, Central Australia, 2017.

Neisseria meningitidis serogroup W has emerged as an increasingly common cause of invasive meningococcal disease worldwide; the average case-fatality rate is 10%. In 2017, an unprecedented outbreak of serogroup W infection occurred among the Indigenous pediatric population of Central Australia; there were 24 cases over a 5-month period. Among these cases were atypical manifestations, including meningococcal pneumonia, septic arthritis, and conjunctivitis. The outbreak juxtaposed a well-resourced healthcare system against unique challenges related to covering vast distances, a socially disadvantaged population, and a disease process that was rapid and unpredictable. A coordinated clinical and public health response included investigation of and empiric treatment for 649 febrile children, provision of prophylactic antimicrobial drugs for 465 close contacts, and implementation of a quadrivalent meningococcal ACWY conjugate vaccine immunization program. The response contained the outbreak within 6 months; no deaths and only 1 case of major illness were recorded.

Models of Governance for Innovation in Medicine and Health Research.

Personalised medicine, digital innovations, and neuro-technologies all offer significant potential benefit for human health and welfare, but also raise complex governance challenges. A variety of approaches have been adopted in the governance of innovative medicines and health technologies, including risk assessment, ethics and self-governance. Recently anticipatory or 'upstream' modes of governance have garnered favour. Anticipatory regulation demands a closer relationship between regulators and innovators, to shape the trajectories of the technology. In the EU context, responsible research and innovation has emerged as a key mechanism of governance. This is linked but distinct from a human rights governance which has the advantage of exerting both legal and moral force. What is needed in the healthcare context are governance models which ensure human rights considerations are taken into account from the earliest stages of innovation, to maximise the likelihood that developments are from the outset beneficial and oriented towards protecting ethical values.

Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized.

Catalogue of inherited disorders found among the Irish Traveller population.

Background Irish Travellers are an endogamous, nomadic, ethnic minority population mostly resident on the island of Ireland with smaller populations in Europe and the USA. High levels of consanguinity result in many rare autosomal recessive disorders. Due to founder effects and endogamy, most recessive disorders are caused by specific homozygous mutations unique to this population. Key clinicians and scientists with experience in managing rare disorders seen in this population have developed a de facto advisory service on differential diagnoses to consider when faced with specific clinical scenarios. Objective(s) To catalogue all known inherited disorders found in the Irish Traveller population. Methods We performed detailed literature and database searches to identify relevant publications and the disease mutations of known genetic disorders found in Irish Travellers. Results We identified 104 genetic disorders: 90 inherited in an autosomal recessive manner; 13 autosomal dominant and one a recurring chromosomal duplication. Conclusion We have collated our experience of inherited disorders found in the Irish Traveller population to make it publically available through this publication to facilitate a targeted genetic approach to diagnostics in this ethnic group.

Presumptive seeding metastasis of pericardial mesothelioma following repeated pericardiocentesis in a dog.

A dog with a history of recurrent pericardial effusion that required repeated pericardiocentesis was presented to the surgical service at the Ontario Veterinary College Health Sciences Centre for thoracoscopic pericardiectomy. Physical examination revealed a subcutaneous mass in the right lateral thorax. Cytology of the subcutaneous mass and histopathology of the pericardium were consistent with mesothelioma. This article details the first reported case of pericardial mesothelioma with suspected extra-thoracic metastasis following pericardiocentesis in a dog.

Implantation métastasique présumée d'un mésothéliome péricardique à la suite de péricardiocentèses répétées chez un chien. Un chien avec une historique d'effusions péricardiques récurrentes qui nécessitaient des péricardiocentèses répétées fut présenté au service de chirurgie du Ontario Veterinary College Health Sciences Centre pour une péricardiectomie thoracoscopique. L'examen physique a révélé une masse souscutanée dans le thorax latéral droit. L'examen cytologique de la masse sous-cutanée et l'histopathologie du péricarde étaient cohérents avec un mésothéliome. Le présent article donne les détails du premier cas rapporté chez un chien de mésothéliome péricardique avec métastase extra-thoracique suspectée consécutive à la suite de péricardiocentèses.(Traduit par Dr Serge Messier).

Treatment outcome of creatine transporter deficiency: international retrospective cohort study.

To evaluate the outcome of current treatment for creatine transporter (CRTR) deficiency, we developed a clinical severity score and initiated an international treatment registry. An online questionnaire was completed by physicians following patients with CRTR deficiency on a treatment, including creatine and/or arginine, and/or glycine. Clinical severity score included 1) global developmental delay/intellectual disability; 2) seizures; 3) behavioural disorder. Phenotype scored 1-3 = mild; 4-6 = moderate; and 7-9 = severe. We applied the clinical severity score pre- and on-treatment. Seventeen patients, 14 males and 3 females, from 16 families were included. Four patients had severe, 6 patients had moderate, and 7 patients had a mild phenotype. The phenotype ranged from mild to severe in patients diagnosed at or before 2 years of age or older than 6 years of age. The phenotype ranged from mild to severe in patients with mildly elevated urine creatine to creatinine ratio. Fourteen patients were on the combined creatine, arginine and glycine therapy. On the combined treatment with creatine, arginine and glycine, none of the males showed either deterioration or improvements in their clinical severity score, whereas two females showed improvements in the clinical severity score. Creatine monotherapy resulted in deterioration of the clinical severity score in one male. There seems to be no correlation between phenotype and degree of elevation in urine creatine to creatinine ratio, genotype, or age at diagnosis. Combined creatine, arginine and glycine therapy might have stopped disease progression in males and improved phenotype in females.

Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.

Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 µmol/L. Nevertheless, we recommend keeping the concentration below 100 µmol/L because levels fluctuate and the complications associated with high levels are so serious.

A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype.

BACKGROUND: Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. METHODS: Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. RESULTS: We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (<9th centile) and similar facial features including a prominent forehead, smooth philtrum and deep-set eyes associated with a recurrent homozygous c.64T>C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. CONCLUSIONS: Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features-particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry-should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations.

The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease.

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors. RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. CONCLUSIONS: The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date.

Assessment of genetic and clinical factors in T2D susceptibility among patients with hypertension.

AIMS: Hypertension (HTN) and Type 2 Diabetes (T2D) often coexist, therefore understanding the relationship between both diseases is imperative to guide targeted prevention/therapy. This study aims to explore the relationship between HTN and T2D using genome-wide association study (GWAS) analysis and biochemical data to understand the implication of both clinical and genetic factors in these pathologies. METHODS: A total of 2,876 patients were enrolled. Using GWAS and biochemical data, patients with both T2D and HTN were compared to patients with only HTN. Specificity was confirmed by testing the detected genetic variants for associations with HTN development in T2D patients, or with HTN in healthy subjects. Regression models were applied to examine the association of T2D in patients with HTN with cardiovascular risk factors. Replication was performed using UK Biobank dataset with 31,170 subjects. RESULTS: Data showed that females with HTN are at higher risk of developing T2D due to dyslipidemia, while males faced higher risk due to high BMI (body mass index) and family history of T2D. GWAS identified Single Nucleotide Polymorphisms (SNPs) linked to T2D in patients with HTN. Notably, rs7865889, rs7756992, and rs10896290 were positively associated with T2D, whereas rs12737517 yielded negative association. Three SNPs were replicated in the UK Biobank (rs10896290, rs7865889, and rs7756992). CONCLUSION: Incorporating clinical and genetic screening into risk assessment is important for the detection and prevention of T2D in patients with HTN. The detected SNPs (rs7865889, rs12737517, and rs10896290), especially the protective SNP (rs12737517), provide an opportunity for better diagnosis, prevention, and therapy of patients with T2D and HTN.

Coronary artery disease patients with rs7904519 (TCF7L2) are at a persistent risk of type 2 diabetes.

AIMS: Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors.This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD. METHODS: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data. RESULTS: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results. CONCLUSIONS: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup.

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients.

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.