Academic journal article Hong Kong Journal of Psychiatry

A Review of Genetic Studies on Attention Deficit Hyperactivity Disorder in Han Chinese Population

Academic journal article Hong Kong Journal of Psychiatry

A Review of Genetic Studies on Attention Deficit Hyperactivity Disorder in Han Chinese Population

Article excerpt

Introduction

Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric problem characterised by hyperactivity, inattention and impulsivity, (1) and has a prevalence rate of 8 to 12% worldwide (2) and 3 to 8% in China. (3-5) Family, twin, and adoption studies provide consistent evidence supporting the hypothesis that genetic factors lead to its familial aggregation. (6,7) For example, Faraone and Biederman (8) found that the risk of ADHD in parents of children with ADHD increased by 2- to 8-fold compared to healthy controls. Sprich et al (9) reported that biological relatives of non-adopted ADHD children had a higher rate of the condition than adoptive relatives, while the risk in adoptive relatives was similar to the relatives of control children. In addition, twin studies concluded that ADHD has high heritability in the range of 75 to 91%. (10,11)

During the past decade, there has been growing interest in molecular genetic studies of ADHD. (12) Moreover, molecular genetic methods including the candidate gene and genome scan approaches have been widely used to explore specific genetic factors by relating variations in DNA (genotype) to the diagnosis of ADHD (phenotype). (13) Previous studies indicated that ADHD is polygenic and multiple genes contribute small fractions to the total genetic effect. (14) Meanwhile, ethnic difference is a common phenomenon in the genetic study in ADHD, (15) which suggests the findings in western settings may not be applicable to other ethnic populations. (10)

To date, the choice of candidate genes has mainly focused on those encoding proteins involving dopaminergic and serotonergic pathways. (10) Findings from numerous studies of ADHD candidate genes have been reviewed in considerable detail elsewhere. (10,16) In this review, we summarise the progress of molecular genetic studies documenting the associations between the candidate genes and variants, and susceptibility to ADHD in the Han Chinese (Table).

Methods

Peer-reviewed articles were searched on Medline and the China National Knowledge Infrastructure database, and references since 1980 were hand-picked.

Results

The Dopamine D4 Receptor Gene

Earlier neuroimaging and neuropsychological studies (12) reported that the dopamine D4 receptor (DRD4) gene (influencing frontal-subcortical networks) is implicated in the pathophysiology of ADHD. Recent studies focused predominantly on a tandem repeat polymorphism in exon III of DRD4 because of one variant, namely the 7-repeat allele that produces a blunted response to dopamine. (17) Faraone et al (18) documented the association between ADHD and DRD4 in a meta-analysis and found the combined estimate of the odds ratios ranged from 1.4 (95% confidence interval [CI], 1.1-1.6) to 1.9 (95% CI, 1.4-2.2), which suggested that there was significant association between ADHD and the 7-repeat allele. Subsequently, a number of studies (though not all) confirmed this association. (19-21) Qian et al (22) investigated the association of the 48bp variable number tandem repeat polymorphism in the DRD4 exon III among Han Chinese children in a case-control study, but did not find the 7-repeat allele in ADHD or healthy control subjects, although 2- and 4-repeat alleles were more common in the ADHD group. Similarly, Leung et al (23) also found a significantly increased prevalence of 2-repeat alleles rather than 7-repeat alleles in 32 Han Chinese children with ADHD. These findings suggest that allele frequencies of the DRD4 gene vary between ethnic groups. (13)

The Dopamine D5 Receptor Gene

Initial studies reported increased transmission of the 148-bp allele to ADHD patients, with the strongest effect in families without a parental history of ADHD, (24) and recent studies on dopamine D5 receptor (DRD5) genes focused on a dinucleotide repeat which maps approximately 18. …

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