Mutation screening of melatonin-related genes in patients with autism spectrum disorders.

BACKGROUND: One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene. METHODS: In the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample. RESULTS: Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A, and MTNR1B. CONCLUSIONS: Our report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.

The dopamine transporter gene (DAT1) polymorphism is associated with premature ejaculation.

INTRODUCTION: Previous research has suggested brain dopamine (DA) neurotransmission to be involved in the control of ejaculation. Furthermore, previous studies indicate a partly hereditary background to premature ejaculation. AIM: To investigate whether the dopamine transporter gene (DAT1) polymorphism is associated with premature ejaculation. METHODS: Retrospective self-reports of four indicators reflecting ejaculatory function-anteportal ejaculation, number of penile thrusts, ejaculation latency time, and feeling of control over ejaculation-and saliva samples for DNA analysis were obtained from 1,290 men (M = 26.9, standard deviation = 4.7 years; range 18-45) with sexual experience. Main Outcome Measures. Calculations of allelic effects were computed using the Generalized Estimating Equations module of SPSS 17. RESULTS: Carriers of the 10R10R genotype had scores indicating a lower threshold to ejaculate on each of the indicators compared to the combined 9R9R/9R10R carrier group. The differences were significant both for the composite score and for anteportal ejaculation, number of thrusts, and feeling of control over ejaculation, but not for ejaculation latency time. The effect of the polymorphism remained significant after controlling for age, homosexual experience, having a regular sexual partner, level of sexual desire, and frequency of sexual activity, hence suggesting that it is not secondary to an association between the studied polymorphism and some other aspect of sexual behavior, but due to a specific influence of DA on ejaculation. CONCLUSIONS: The findings of the present study support results of previous studies indicating involvement of dopaminergic neurotransmission in ejaculation.