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1.
Wallis D Arcos-Burgos M Jain M Castellanos FX Palacio JD Pineda D Lopera F Stanescu H Pineda D Berg K Palacio LG Bailey-Wilson JE Muenke M 《Attention deficit and hyperactivity disorders》2009,1(1):19-24
The neural nicotinic acetylcholine receptor α4 subunit (CHRNA4), at 20q13.2-q13.3, is an important candidate gene for conferring susceptibility to attention deficit/hyperactivity disorder (ADHD). Several studies have already looked for association/linkage between ADHD and CHRNA4 in different populations. We used the Pedigree Disequilibrium Test to search for evidence of association between ADHD and six SNP marker loci in families from the isolated Paisa population. We found that the T allele of SNP rs6090384 exhibits a deficit of transmission in unaffected individuals (OR = 5.43, IC 1.54-19.13) (global P value = 0.014). We also found significant association and linkage to extended haplotypes rs2273502-rs6090384 (combination of variants C-T, respectively) (P = 0.02) and rs6090384-rs6090387 (P = 0.04) (combination of variants T-G, respectively). SNP rs6090384, variant T, has also been reported to be associated with inattention in a previous study. This makes ours the ninth study to examine the association of CHRNA4 with ADHD and the seventh one to find evidence for association in a population with a different ethnicity. 相似文献
2.
A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men 总被引:14,自引:0,他引:14
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Feng Y Niu T Xing H Xu X Chen C Peng S Wang L Laird N Xu X 《American journal of human genetics》2004,75(1):112-121
Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men. 相似文献
3.
Luciana Tovo-Rodrigues Luis A. Rohde Ana M. B. Menezes Guilherme V. Polanczyk Christian Kieling Julia P. Genro Luciana Anselmi Mara H. Hutz 《PloS one》2013,8(12)
The dopamine receptor D4 (DRD4) is one of the most studied candidate genes for Attention-Deficit/Hyperactivity Disorder (ADHD). An excess of rare variants and non-synonymous mutations in the VNTR region of 7R allele in ADHD subjects was observed in previous studies with clinical samples. We hypothesize that genetic heterogeneity in the VNTR is an important factor in the pathophysiology of ADHD. The subjects included in the present study are members of the 1993 Pelotas Birth Cohort Study (N=5,249). We conducted an association study with the 4,101 subjects who had DNA samples collected. The hyperactivity-inattention scores were assessed through the parent version of the Strengths and Difficulties Questionnaire at 11 and 15 years of age. The contribution of allele’s length and rare variants to high hyperactivity/inattention scores predisposition was evaluated by multivariate logistic regression. No effect of allele length was observed on high scores of hyperactivity-inattention. By contrast, when resequencing/haplotyping was conducted in a subsample, all 7R rare variants as well as non-synonymous 7R rare variants were associated with high hyperactivity/inattention scores (OR=2.561; P=0.024 and OR=3.216; P=0.008 respectively). A trend for association was observed with 4R rare variants. New coding mutations covered 10 novel motifs and many of them are previously unreported deletions leading to different stop codons. Our findings suggest a contribution of DRD4 7R rare variants to high hyperactivity-inattention scores in a population-based sample from a large birth cohort. These findings provide further evidence for an effect of DRD4 7R rare variants and allelic heterogeneity in ADHD genetic susceptibility. 相似文献
4.
多巴胺D4受体基因与注意缺损多动障碍 总被引:6,自引:1,他引:5
为探讨注意缺损多动障碍(ADHD)与多巴胺D4受体基因(dopamine D4 receptor gene,DRD4)间的关系,采用Amp-FLP的方法检测了上海地区汉族人群中68例ADHD患及其父母DRD4的多态性,数据采用基于单体型的单体型相对风险(HHRR)及传递不平衡检验(TDT)进行遗传关联分析。结果表明HHRR分析和复等位基因的TDT检验,均未显示出与ADHD的遗传关联性(P>0.05)。提示上海地区人群中DRD4基因与ADHD无显性关联。 相似文献
5.
Judit Lazary Peter Dome Iren Csala Gabor Kovacs Gabor Faludi Mari Kaunisto Balazs Dome 《PloS one》2014,9(1)
Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment-seeking smokers was investigated after overnight nicotine abstinence. Alpha4 nicotinic acetylcholine receptor (nAChR) subunit-related phenotypes were assessed by the Fagerström Test for Nicotine Dependence (FTND), exhaled carbon monoxide (CO) measurements, the Minnesota Nicotine Withdrawal Scale (MNWS) and the Zung Self-Rating Depression Scale (ZSDS). Seven tag SNPs (single-nucleotide polymorphisms) across CHRNA4 (the gene encoding alpha4 subunit of the nicotinic acetylcholine receptor) were genotyped and two-step cluster analysis was used for phenotypic cluster characterization. Haplotype estimation was determined by HapStat module of R 2.0 software. Three different phenotypic clusters were identified and the C3 cluster was characterized by the highest ZSDS and MNWS scores compared to others. Furthermore, lifetime prevalence of major depression was significantly higher in the C3 cluster (p = 0.019). In genetic association tests, this cluster was also significantly associated with rs3787138 genotypes (p = 0.004) while haplotype analyses of three SNPs (rs3787138, rs1044396, rs3787140) revealed that the risk for C3 phenotype was almost three times higher in GCC haplotype carriers compared to others (pperm = 0.013). This is the first report on a significant association between CHRNA4 variants and a subgroup of smokers characterized by massive withdrawal symptoms and affective vulnerability. Identification of such a phenotypic cluster can be a pivotal step for further pharmacogenetic studies on ligands of the alpha4 nAChR subunit. Our results suggest that performing cluster analysis in genetic association studies can be proposed for complex disorders. 相似文献
6.
H. M. Kamens R. P. Corley M. B. McQueen M. C. Stallings C. J. Hopfer T. J. Crowley S. A. Brown J. K. Hewitt M. A. Ehringer 《Genes, Brain & Behavior》2013,12(3):297-304
Nicotine binds to nicotinic acetylcholine receptors and studies in animal models have shown that α4β2 receptors mediate many behavioral effects of nicotine. Human genetics studies have provided support that variation in the gene that codes for the α4 subunit influences nicotine dependence (ND), but the evidence for the involvement of the β2 subunit gene is less convincing. In this study, we examined the genetic association between variation in the genes that code for the α4 (CHRNA4) and β2 (CHRNB2) subunits of the nicotinic acetylcholine receptor and a quantitative measure of lifetime DSM‐IV ND symptom counts. We performed this analysis in two longitudinal family‐based studies focused on adolescent antisocial drug abuse: the Center on Antisocial Drug Dependence (CADD, N = 313 families) and Genetics of Antisocial Drug Dependence (GADD, N = 111 families). Family‐based association tests were used to examine associations between 14 single nucleotide polymorphisms (SNPs) in CHRNA4 and CHRNB2 and ND symptoms. Symptom counts were corrected for age, sex and clinical status prior to the association analysis. Results, when the samples were combined, provided modest evidence that SNPs in CHRNA4 are associated with ND. The minor allele at both rs1044394 (A; Z = 1.988, P = 0.047, unadjusted P‐value) and rs1044396 (G; Z = 2.398, P = 0.017, unadjusted P‐value) was associated with increased risk of ND symptoms. These data provide suggestive evidence that variation in the α4 subunit of the nicotinic acetylcholine receptor may influence ND liability. 相似文献
7.
Attention-deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by symptoms of inattention, impulsivity and hyperactivity that adversely affect many aspects of life. Whereas the etiology of ADHD remains unknown, growing evidence indicates a genetic involvement in the development of this disorder. The brain circuits associated with ADHD are rich in monoamines, which are involved in the mechanism of action of psychostimulants and other medications used to treat this disorder. Dopamine (DA) is believed to play a major role in ADHD but other neurotransmitters are certainly also involved. Genetically modified mice have become an indispensable tool used to analyze the contribution of genetic factors in the pathogenesis of human disorders. Although rodent models cannot fully recapitulate complex human psychiatric disorders such as ADHD, transgenic mice offer an opportunity to directly investigate in vivo the specific roles of novel candidate genes identified in ADHD patients. Several knock-out and transgenic mouse models have been proposed as ADHD models, mostly based on targeting genes involved in DA transmission, including the gene encoding the dopamine transporter (DAT1). These mutant models provided an opportunity to evaluate the contribution of dopamine-related processes to brain pathology, to dissect the neuronal circuitry and molecular mechanisms involved in the antihyperkinetic action of psychostimulants and to evaluate novel treatments for ADHD. New transgenic models mouse models targeting other genes have recently been proposed for ADHD. Here, we discuss the recent advances and pitfalls in modeling ADHD endophenotypes in genetically altered animals. 相似文献
8.
Ribasés M Ramos-Quiroga JA Sánchez-Mora C Bosch R Richarte V Palomar G Gastaminza X Bielsa A Arcos-Burgos M Muenke M Castellanos FX Cormand B Bayés M Casas M 《Genes, Brain & Behavior》2011,10(2):149-157
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable developmental disorder characterized by a persistent impairing pattern of inattention and/or hyperactivity-impulsivity. Using families from a genetic isolate, the Paisa population from Colombia, and five independent datasets from four different populations (United States, Germany, Norway and Spain), a highly consistent association was recently reported between ADHD and the latrophilin 3 (LPHN3) gene, a brain-specific member of the LPHN subfamily of G-protein-coupled receptors that is expressed in ADHD-related regions, such as amygdala, caudate nucleus, cerebellum and cerebral cortex. To replicate the association between LPHN3 and ADHD in adults, we undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single- and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P = 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P = 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan. 相似文献
9.
以往研究表明,儿茶酚胺系统可能参于注意缺损多动障碍(attention—deficit hyperactivityity disorder,ADHD)的发生,而儿茶酚胺-O-甲基转移酶(catechel—O—methyltransferase,COMT)是一种降解多巴胺和去甲肾上腺素系统的儿茶酚胺神经递质的酶。因此,采用两种以家系为基础的分析方法,即传递不平衡实验(transmission disequilibrium test,TDT)和单倍型为基础的单倍型相对风险率(haplotype—based haplotype relative risk,HHRR)去探讨COMT和中国人群中79个ADHD核心家系的关联性,ADHD诊断符合DSM—IV的诊断标准。TDT(X^2=1.03,df=1,P〉0.05)和HHRR(X^2=1.08,df=1,P〉0.05)两种方法的分析结果表明,COMT等位基因不能优先传递给ADHD儿童,提示在中国人群中ADHD与COMT基因无关联性。 相似文献
10.
Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24. 总被引:17,自引:0,他引:17
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H A Phillips I E Scheffer K M Crossland K P Bhatia D R Fish C D Marsden S J Howell J B Stephenson J Tolmie G Plazzi O Eeg-Olofsson R Singh I Lopes-Cendes E Andermann F Andermann S F Berkovic J C Mulley 《American journal of human genetics》1998,63(4):1108-1116
Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis. 相似文献
11.
The cholinergic receptor, nicotinic, alpha 4 (CHRNA4) gene encodes the neuronal nicotinic acetylcholine receptor alpha-4 subunit. Recent research has shown that a variation in CHRNA4 (rs1044396) affects attention and negative emotionality in normal adults. To determine the link between CHRNA4 variation and cognitive function/depressed mood, this study conducted a genotype-phenotype correlation analysis between the common CHRNA4:rs1044396 variant and several baseline parameters of cognition and depressed mood in 192 elderly male subjects without major psychiatric disorders or dementia. Study findings identified a significant link between the CHRNA4:rs1044396 polymorphism and depression and loneliness in the aged. Compared to carriers of at least one T-allele, carriers of the homozygous C/C genotype described themselves as more depressed and lonely. This is the first evidence which may implicate CHRNA4 in depressed emotions in the elderly. 相似文献
12.
Introduction
The aim of the study was to assess the association between attention deficit/hyperactivity disorder (ADHD) symptoms and potentially obesogenic behaviors.Methods
Data of 11,676 German children and adolescents (6–17 years) were analyzed. Television/video exposure, physical activity, food frequency and portion size were assessed using questionnaires. A dietary quality index, energy density and volumes of consumed food, and total energy intake were calculated. The parent-rated hyperactivity/inattention subscale of the Strengths and Difficulties Questionnaire (SDQ-HI) was used as a continuous measure of ADHD symptoms. Associations were analyzed with general linear models adjusting for sex, age, socioeconomic status, migrant status, parental BMI, and parental smoking.Results
SDQ-HI scores correlated positively with physical activity, average energy density of food, volume of beverages, total energy intake, and television exposure and negatively with the nutritional quality score (HuSKY) even after adjustment for parental variables (BMI, smoking, socioeconomic status, migrant status), age, sex, as well as the other SDQ subscales. The adjusted association of the SDQ-HI scores with the nutritional quality score was stronger in girls and the associations with food volume, food energy, and total energy intake was significant only in girls.Conclusions
Poor nutritional quality, high energy intake and television exposure appear to be independently associated with ADHD symptoms. The relationship between food energy intake and ADHD symptoms was especially pronounced in girls and this may help to explain the reported association of ADHD symptoms with overweight in adolescent girls. 相似文献13.
《Biomarkers》2013,18(7):513-522
Several lines of evidence support the role of monoaminergic and cholinergic dysregulation in attention deficit hyperactivity disorder (ADHD) and the concept that peripheral blood neurotransmission indices may represent valuable surrogate CNS markers. We determined platelet MAO-B activity (p-MAO-B) and lymphocyte muscarinic cholinergic receptor binding (l-MR) in 44 unmedicated ADHD children (aged 9.1?±?2.87 years) and in 26 age-matched controls for comparison. Lower levels of p-MAO-B (~35%) and l-MR (~55%) in ADHD were observed compared with controls. Differences were gender-dependent: p-MAO-B was reduced in males only (5.20?±?2.99 vs 8.46?±?5.1 nmol mg?1 protein h?1 in ADHD and controls, respectively) and l-MR in females only (ADHD vs control: 6.63?±?1.75 and 15.30?±?8.35?fmol 10?6 cells). The clinical significance was corroborated by the correlation between these markers and severity of specific symptoms: lower p-MAO-B associated with increased inattention scores (Conners’ teacher-rating scale); lower l-MR associated with increased score for oppositional-defiant disorder (ODD) (SNAP-IV); and trend towards correlation between increased inattention (SNAP-IV) and lower l-MR. 相似文献
14.
Eyup Sabri Ercan Ulku Akyol Ardic Burge Kabukcu Basay Elif Ercan Omer Basay 《Attention deficit and hyperactivity disorders》2013,5(4):377-385
The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 1994, American Psychiatric Association) describes attention deficit hyperactivity disorder (ADHD) as a heterogeneous disorder; providing diagnostic criteria for three subtypes: hyperactive/impulsive (ADHD/HI), inattentive (ADHD/I), and combined type (ADHD/C). Differences among the subtypes are well defined, but there may be also differences in terms of treatment responses. The aim of this study is to assess the responses of ADHD/I and ADHD/C to atomoxetine treatment. The medical records of the January–June 2012 term, first time referrals to outpatient clinic, were reviewed, and 37 ADHD diagnosed primary school age children (18 ADHD/I, 19 ADHD/C) that were treated with atomoxetine were determined. Thirty-five of them who completed 8 weeks of treatment duration were recruited for the study. The children with an ADHD medication use history in 2 months time prior to onset of treatment and/or the children receiving additional psychopharmacologic treatment to atomoxetine were excluded. Baseline and eighth week assessment, records were evaluated. Efficacy assessments included Turgay DSM-IV ADHD Screening and Rating Scale parent and teacher forms (T-DSM-IV) and Clinical Global Impression Scale-Severity and Improvement subscales. Safety assessments included laboratory and body weight assessments, ECG, heart rate, and blood pressure evaluations (baseline and eighth week) along a scale filled by the parents at the eighth week to review side effects. Atomoxetine was found to be effective in both ADHD/I and ADHD/C groups. Atomoxetine also decreased the opposition defiance subscale scores of T-DSM-IV (both parent and teacher forms), whereas it was not found to make statistically significant difference in the conduct disorder subscale scores. Mean difference in 8-week time in T-DSM-IV hyperactivity subscale and total scores of parent and teacher forms; inattention subscale scores of only parent forms and the CGI- severity subscale scores; differed significantly among the ADHD/I and ADHD/C groups; that ADHD/C types responded better to medication. Results of this study revealed that atomoxetine is effective both in ADHD/I and ADHD/C subtypes. ADHD/C types may be responding better to atomoxetine treatment than the ADHD/I subtypes. 相似文献
15.
Neurotrophins (NTs), a family of proteins including nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4, are essential for neural growth, survival, and differentiation, and are therefore crucial for brain development. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by problems of inattention and/or hyperactivity-impulsivity. ADHD is one of the most common childhood onset psychiatric disorders. Studies have suggested that both genetic and environmental factors influence the development of the disorder, although the precise causes of ADHD have not yet been identified. In this review, we assess the role of NTs in the pathophysiology of ADHD. Preclinical evidence indicates that BDNF knockout mice are hyperactive, and an ADHD rodent model exhibited decreased cerebral BDNF levels. Several lines of evidence from clinical studies, including blood level and genetic studies, have suggested that NTs are involved in the pathogenesis of ADHD and in the mechanism of biological treatments for ADHD. Future directions for research are proposed, such as using blood NTs as ADHD biomarkers, optimizing NT genetic studies in ADHD, considering NTs as a link between ADHD and other comorbid mental disorders, and investigating methods for optimally modulating NT signaling to discover novel therapeutics for treating ADHD. 相似文献
16.
Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes 总被引:15,自引:0,他引:15
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Lowe N Kirley A Hawi Z Sham P Wickham H Kratochvil CJ Smith SD Lee SY Levy F Kent L Middle F Rohde LA Roman T Tahir E Yazgan Y Asherson P Mill J Thapar A Payton A Todd RD Stephens T Ebstein RP Manor I Barr CL Wigg KG Sinke RJ Buitelaar JK Smalley SL Nelson SF Biederman J Faraone SV Gill M 《American journal of human genetics》2004,74(2):348-356
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes. 相似文献
17.
Yang Wang Haijian Wu Qiji Liu Cuihong Wang Lei Fu Han Wang Wenjie Zhu Weijiang Fu Yajuan Lv Shikun Wang Likuan Hu 《PloS one》2013,8(7)
Background
CHRNA5-A3-B4, the gene cluster encoding nicotinic acetylcholine receptor subunits, is associated with lung cancer risk and smoking behaviors in people of European descent. Because cigarette smoking is also a major risk factor for esophageal squamous cell carcinoma (ESCC), we investigated the associations between variants in CHRNA5-A3-B4 and ESCC risk, as well as smoking behaviors, in a Chinese population.Methods
A case-control study of 866 ESCC patients and 952 healthy controls was performed to study the association of polymorphisms (rs667282 and rs3743073) in CHRNA5-A3-B4 with cancer risk using logistic regression models. The relationships between CHRNA5-A3-B4 polymorphisms and smoking behaviors that can be quantified by cigarettes smoked per day (CPD) and pack-years of smoking were separately estimated with Kruskal-Wallis tests among all 840 smokers.Results
CHRNA5-A3-B4 rs667282 TT/TG genotypes were associated with significantly increased risk of ESCC [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.03 – 1.69, P = 0.029]. The increased ESCC risk was even higher among younger subjects (≤60 years) (OR = 1.44, 95% CI = 1.04 – 1.98, P = 0.024). These effects were not found in another polymorphism rs3743073. No evident association between the two polymorphisms and smoking behaviors was observed.Conclusions
These results support the hypothesis that CHRNA5-A3-B4 is a susceptibility gene cluster for ESCC. The relationship between CHRNA5-A3-B4 and smoking behaviors in a Chinese population needs further investigation. 相似文献18.
Adel E. El-Tarras Adnan A. Alsulaimani Nabil S. Awad Nahla Mitwaly Manal M. Said Ayman M. Sabry 《Molecular biology reports》2012,39(12):11081-11086
Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4?%. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30?bp-promoter VNTR and DAT1 40?bp 3′ UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95?% confidence interval (95?% CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P?<?0.01, OR?=?3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P?<?0.01, OR?=?2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P?<?0.01, OR?=?4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia. 相似文献
19.
Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to
the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been
made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of
candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review
of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies.
The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might
suggest moderating variables that could explain inconsistent results. Significant associations were identified for several
candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender,
exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant
to future studies of the genetics of ADHD. 相似文献
20.
Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism 总被引:9,自引:0,他引:9
Smalley SL Kustanovich V Minassian SL Stone JL Ogdie MN McGough JJ McCracken JT MacPhie IL Francks C Fisher SE Cantor RM Monaco AP Nelson SF 《American journal of human genetics》2002,71(4):959-963
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a genetic etiology of the disorder, although putative alleles, principally in dopamine-related pathways suggested by candidate-gene studies, have very small effect sizes. We use affected-sib-pair analysis in 203 families to localize the first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13 (maximum LOD score 4.2; P=.000005), building upon an earlier genomewide scan of this disorder. The region overlaps that highlighted in three genome scans for autism, a disorder in which inattention and hyperactivity are common, and physically maps to a 7-Mb region on 16p13. These findings suggest that variations in a gene on 16p13 may contribute to common deficits found in both ADHD and autism. 相似文献