Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD

During the past 15 years, an impressive amount of genetic information has become available in the research field of psychiatry, particularly as it relates to attentiondeficit/ hyperactivity disorder (ADHD). However, the classical clinical approach to ADHD has minimally affected and not significantly been improved by this genetic revolution. It is difficult to predict how long it will take for genetic findings to alter the way clinicians treat patients with ADHD. New medications or treatment protocols may take years to become routine clinical practice. However, when taken together, recent successes in genomics, pharmacogenomics, and genetic epidemiology have the potential (1) to prevent comorbid consequences of ADHD, (2) to individualize therapies for patients with ADHD, and (3) to define new epidemiological policies to aid with the impact of ADHD on society. Here, we present an overview of how genetic research may affect and improve the quality of life of patients withADHD: as an example, we use the discovery of LPHN3, a new gene in which variants have recently been shown to be associated with ADHD

Análisis de polimorfismos TAP1 y TAP2 en pacientes del noroeste de Colombia con lupus eritematoso sistémico

Objective: To determine the influence of TAP1 and TAP2 alleles in northwestern Colombian patients with systemic lupus erythematosus (SLE). Methods: Unselected patients with SLE (n=140) and controls (n=120) matched for sex, age, and ethnicity were analysed. Clinical manifestations, clinical activity, and severity of disease were recorded. Autoantibodies were detected by enzyme linked immunosorbent assay (ELISA). TAP1 and TAP2 polymorphisms were determined by amplification refractory mutation system-polymerase chain reaction. A Hardy-Weinberg equilibrium test, microdifferentiation analysis, linkage disequilibrium analysis, and haplotype and allele frequency comparisons were performed. Results: The TAP2 variant Val379/Ala565/Ala665 (allele TAP2*0201) was associated with SLE (56% v 39%; odds ratio=2, 95% confidence interval 1.22 to 3.30, pc=0.03). There was no stratification between patient and control samples. Linkage disequilibrium between TAP1 and TAP2 loci was found in controls but not in patients. An excess in the number of heterozygotes in the TAP2 locus was found in patients. No association between TAP1 and TAP2 variants and the presence of autoantibodies, clinical expression, or severity of disease was found. Conclusions: The TAP2 locus influences susceptibility to SLE in our patient group; however, it has no significant effect on the immune response or on the clinical course of the disease

Análisis de polimorfismos TAP1 y TAP2 en pacientes del noroeste de Colombia con lupus eritematoso sistémico

Objective: To determine the influence of TAP1 and TAP2 alleles in northwestern Colombian patients with systemic lupus erythematosus (SLE). Methods: Unselected patients with SLE (n=140) and controls (n=120) matched for sex, age, and ethnicity were analysed. Clinical manifestations, clinical activity, and severity of disease were recorded. Autoantibodies were detected by enzyme linked immunosorbent assay (ELISA). TAP1 and TAP2 polymorphisms were determined by amplification refractory mutation system-polymerase chain reaction. A Hardy-Weinberg equilibrium test, microdifferentiation analysis, linkage disequilibrium analysis, and haplotype and allele frequency comparisons were performed. Results: The TAP2 variant Val379/Ala565/Ala665 (allele TAP2*0201) was associated with SLE (56% v 39%; odds ratio=2, 95% confidence interval 1.22 to 3.30, pc=0.03). There was no stratification between patient and control samples. Linkage disequilibrium between TAP1 and TAP2 loci was found in controls but not in patients. An excess in the number of heterozygotes in the TAP2 locus was found in patients. No association between TAP1 and TAP2 variants and the presence of autoantibodies, clinical expression, or severity of disease was found. Conclusions: The TAP2 locus influences susceptibility to SLE in our patient group; however, it has no significant effect on the immune response or on the clinical course of the disease

A new method for detecting significant p-values with applications to genetic data [Una nuevo mtodo para la deteccin de valores p significativos y su aplicacin a datos genticos]

A new method for detecting significant p-values is described in this paper. This method, based on the distribution of the m-th order statistic of a U(0; 1) distribution, is shown to be suitable in applications where m → ∞ independent hypothesis are t

From the black widow spider to human behavior: Latrophilins, a relatively unknown class of G protein-coupled receptors, are implicated in psychiatric disorders

The findings of a recent study associate LPHN3, a member of the latrophilin family, with an increased risk of developing attention deficit/hyperactivity disorder (ADHD), the most common psychiatric disorder in childhood and adolescence. Latrophilins comprise a new family of G protein-coupled receptors of unknown native physiological function that mediate the neurotoxic effects of α-latrotoxin, a potent toxin found in black widow spider venom. This receptor-toxin interaction has helped to elucidate the mechanistic aspects of neurotransmitter and hormone release in vertebrates. Such unprecedented discovery points to a new direction in the assessment of ADHD and suggest that further study of this receptor family may provide novel insights into the etiology and treatment of ADHD and other related psychiatric conditions

Caracterización molecular del polimorfismo de los genes Tap1 yTap2 en pacientes con síndrome de sjogren

IP 2213-04-1022-98Incluye anexos.Colombiana. -- Vol. 25, no. 1 (ene.-feb. 2001). -- Polymorphismof TAP1 and TAP2 genes in systemic lupus;erythematosus (SLE): Tap2- 0201 is a susceptibility markerinaColombianpopulation / Paula Andrea Correa;Vanegas. ... [et. al]. -- En: American Collage of Rheumatology.-- Vol. 43, no. 9 (Sep. 2000); p. 360.;PONECIA(S) EN CONGRESO: Analisis molecular de los alelos HLA-DRasociadosa la susceptibilidad de la;Artritis Reumatoidea (AR) / Juan Manuel Amaya,Paula AndreaCorrea. -- En:Congreso Colombiano de Genetica;Medica (4 : 2000 : Popayan). -- Popayan, 2000. p. -- 28 cm. --The sharedepitope (SE) QRRAA and TAP2*0201;allele contribute to rheumatoid arthritis (RA) susceptibilityina Colombian population / Paula Andrea Correa,;Juan Manuel Anaya. -- En: American College Of Rheumatology/ Annual Scientific Meeting (64 2000 :;Philadelphia: Lippincott Williams & Wilkins). -- Philadelphia,2000. -- p.-- 28 cm. -- ARTICULO(S) EN;REVISTA: Polimorfismo de genes TAP1 yTAP2 en pacientes conlupuseritematoso sistemico: TAP2 - 0201 es un;marcador de susceptibilidad / Paula Andrea Correa Vanegas....[et. al]. -'- en: Revista Acta Medic

Pharmacogenetic Impact of VKORC1 and CYP2C9 allelic variants on warfarin dose requirements in a hispanic population isolate

Warfarin is the most prescribed oral anticoagulant worldwide. Because of the complexity of warfarin therapy, we attempted to dissect genetic from bioenvironmental factors influencing warfarin dose responses in individuals of a genetic isolate of Hispani

REPRODUCTIVE SUCCESS IS PREDICTED BY SOCIAL DYNAMICS AND KINSHIP IN MANAGED ANIMAL POPULATIONS

Kin and group interactions are important determinants of reproductive success in many species. Their optimization could, therefore, potentially improve the productivity and breeding success of managed populations used for agricultural and conservation purposes. Here we demonstrate this potential using a novel approach to measure and predict the effect of kin and group dynamics on reproductive output in a well-known species, the meerkat Suricata suricatta. Variation in social dynamics predicts 30% of the individual variation in reproductive success of this species in managed populations, and accurately forecasts reproductive output at least two years into the future. Optimization of social dynamics in captive meerkat populations doubles their projected reproductive output. These results demonstrate the utility of a quantitative approach to breeding programs informed by social and kinship dynamics. They suggest that this approach has great potential for improvements in the management of social endangered and agricultural species

ADHD latent class clusters: DSM-IV subtypes and comorbidity

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6-18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding