Association between SYP with attention-deficit/hyperactivity disorder in Chinese Han subjects: Differences among subtypes and genders

Dysfunction of neurotransmitters has been suggested to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD). Hence, genes encoding proteins involved in the vesicular release process of those neurotransmitters are attractive candidates in ADHD genetics. One of these genes is SYP, which encodes synaptophysin, a protein known to participate in regulating neurotransmitter release and synaptic plasticity. Several studies have reported an association between SYP and ADHD, but more work is needed to refine the association. In the present study, we attempt to investigate their association in Chinese Han subjects by family-based and case-control studies. Transmission disequilibrium tests (TDTs) in 1112 trios found significant association between SYP and the predominantly inattentive subtype (ADHD-I), especially for males with ADHD-I, both from single nucleotide polymorphism (SNP) and haplotypic analyses. Chi-square tests in 1682 ADHD probands and 957 comparison subjects indicated possible association of SYP with female ADHD and female ADHD-I. However, the associated alleles and haplotypes between males and females were reversed. In conclusion, our results suggested that SYP may be primarily associated with ADHD-I and its genetic mechanism may be gender-specific. Thus, it is necessary to take subtype and gender into account in ADHD genetic studies.