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

Impact of Early Nutrition on Body Composition in Children Aged 9.5 Years Born with Extremely Low Birth Weight

To evaluate body composition, metabolism and growth as well as their interaction with early nutrition in former extremely low birth weight infants (ELBW), we assessed qualitative and quantitative nutritional intake during initial hospitalization and infantile growth parameters in 61 former ELBW infants with a birth weight &lt;1000 g. In two follow-up exams, physical and biochemical development were measured at 5.7 and at 9.5 years. At the second follow-up, in addition to biochemical reassessment, body composition was analyzed by dual-energy x-ray absorptiometry (DEXA). Protein intake between birth and discharge was associated with weight gain in the first six months of life (r = 0.51; p &lt; 0.01). Weight catch-up preceded height catch-up. Protein intake in early infancy correlated highly significantly with abdominal fat mass (r = 0.49; p &lt; 0.05), but not with lean body mass at 9.5 years (r = 0.30; not significant (n.s.). In contrast to nutrient intake, birth weight was associated with lean body mass (r = 0.433; p &lt; 0.001). Early protein and carbohydrate intake were associated with high-density lipoprotein (HDL)-cholesterol, and early catch-up growth correlated with fasting insulin at follow-up. Stepwise linear regression demonstrated that protein intake predicted fat mass (p &lt; 0.05), whereas only gender and birth weight standard deviation score (SDS) contributed significantly to lean body mass variation (p &lt; 0.05). Our results suggest an important impact of early nutrient intake on body composition and metabolism in later childhood in ELBW children