Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors. Recently, a common 44-bp deletion in the promoter ...region of the serotonin transporter (5-HTTLPR) that results in reduced transcription and lower transporter protein levels was described. Toward unraveling a possible role of the 5-HTTLPR polymorphism in childhood disruptive behaviors, we examined this gene in attention deficit hyperactivity disorder (ADHD), a heterogeneous childhood disorder in which three phenotypes are recognized by DSM IV criteria: inattentive (type I), hyperactive-impulsive (type II), and combined type (type III). By using the haplotype relative risk design, a group of 98 triads (both parents and proband child) were tested for a possible association between 5-HTTLPR and ADHD. A significant decrease in the short/short 5-HTTLPR genotype was observed in the ADHD type III combined group (10.29% vs. 30.88%) compared with the HRR-derived control group (likelihood ratio = 9.62, P = 0.008, n = 68 triads). Similar results were observed when allele frequencies were compared (likelihood ratio = 3.81, P = 0.05, n = 136 alleles). These first findings should be interpreted cautiously until replicated in independently recruited clinical samples.
The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to reside within a region around human leukocyte antigen-C spanning 250 kb, termed risk haplotype (RH) 1/2. By re-analyzing a ...published data set with a previously developed method, the haplotype sharing statistic, we confirm localization of PSORS1 to the RH1 region and refine its location to marker M6S168. We replicate this result in an independent patient sample. The target region harbors fragments of a human endogenous retrovirus K (HERV-K) endogenous retrovirus. Two single-nucleotide polymorphisms with alleles differing between high- and low-risk haplotypes are located within the HERV-K dUTPase. One of these encodes a predicted non-conserved Glu–Arg exchange. The HERV-K dUTPase is expressed in peripheral blood and in normal as well as lesional psoriatic skin. Our results indicate that an endogenous retroviral dUTPase constitutes a candidate gene for the PSORS1 mutation.
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