Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults

<p>Abstract</p> <p>Background</p> <p>Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial.</p> <p>Methods</p> <p>We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay.</p> <p>Results</p> <p>Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability.</p> <p>Conclusion</p> <p>The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.</p

Adult attention deficit hyperactivity disorder is associated with migraine headaches

Attention deficit hyperactivity disorder (ADHD) is now recognized as a common disorder both in child and adult psychiatry. Adult patients with a diagnosis of ADHD (n = 572) and community controls (n = 675) responded to auto-questionnaires rating past and present symptoms of ADHD, co-morbid conditions, including migraine, treatment history and work status. The prevalence of migraine was significantly higher in the patient group compared to the controls (28.3% vs. 19.2%, P < 0.001, OR = 1.67, CI 1.28–2.17). The difference from controls was particularly marked for men (22.5% vs. 10.7%, P < 0.001, OR = 2.43, CI 1.51–3.90) but was also significant for women (34.4% vs. 24.9%, P = 0.008, OR = 1.58, CI 1.13–2.21). In both patients and controls, migraine was associated with symptoms of mood and anxiety disorders. These findings point to a co-morbidity of migraine with ADHD, and it is possible that these patients represent a clinical and biological subgroup of adult patients with ADHD

Epistasis between COMT and MTHFR in Maternal-Fetal Dyads Increases Risk for Preeclampsia

Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C→T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor “T” allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR

Adult attention deficit hyperactivity disorder is associated with asthma

<p>Abstract</p> <p>Background</p> <p>Attention deficit hyperactivity disorder (ADHD) is increasingly recognized as a common disorder not only in children, but also in the adult population. Similarly, asthma also has a substantial prevalence among adults. Previous studies concerning a potential relationship between ADHD and asthma have not presented consistent results.</p> <p>Methods</p> <p>A cross-sectional study of 594 adult patients diagnosed with ADHD, compared with 719 persons from the general population. Information was collected between 1997 and 2005 using auto-questionnaires rating past and present symptoms of ADHD, co-morbid conditions, including asthma, and work status.</p> <p>Results</p> <p>The prevalence of asthma was significantly higher in the ADHD patient group compared to the controls, 24.4% vs. 11.3% respectively (OR = 2.54, 95% CI 1.89-3.44), and controls with asthma scored higher on ratings of both past and present symptoms of ADHD. Female ADHD patients had a significantly higher prevalence of asthma compared to male ADHD patients (30.9% vs. 18.2%, OR = 2.01, CI 1.36-2.95), but in controls a slight female preponderance was not statistically significant. In both ADHD patients and controls, having asthma was associated with an increased prevalence of symptoms of mood- and anxiety disorders.</p> <p>Conclusions</p> <p>The present findings point to a co-morbidity of ADHD and asthma, and these patients may represent a clinical and biological subgroup of adult patients with ADHD.</p

Polythelia in a 13-year old girl

We present a rare case of a 13-year old girl with a bilateral polythelia. We would like to draw attention to this particular mammary malformation