Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Adenauerallee 119, Bonn 53113, Germany.
BMC Med Genet. 2011 Sep 1;12:115. doi: 10.1186/1471-2350-12-115.
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.
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.
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.
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.
儿茶酚-O-甲基转移酶（COMT）在多巴胺和雌激素代谢中起着关键作用。最近，有研究报道，COMT 单倍型而非单一多态性 Val158Met 通过调节 mRNA 二级结构，对蛋白表达的差异起作用。迄今为止，研究 COMT（可溶性 COMT）启动子区域的表观遗传变异性主要集中在表型方面，且结果存在争议。
我们评估了 20 对单卵双胞胎（平均年龄 4 岁）唾液和血液中 S-COMT 启动子区域的甲基化，这些双胞胎因严重的胎儿-胎儿输血综合征而导致宫内发育不同。由于 COMT 基因型的差异，我们对 rs6269、rs4633 和 rs4680（Val158Met）多态性的产前和产后生长进行了分析。使用定量 SIRPH（SNuPE-IP RP HPLC）测定法，测定了两个先前报道的部分甲基化胞嘧啶的甲基化水平。
总的来说，我们观察到 S-COMT 启动子甲基化的高度变异性，但与个体的产前或产后生长模式的差异没有相关性。然而，在双胞胎中，我们注意到了一种明显的相似性，这可能与潜在的 COMT 基因型有关。这种关联在 93 名无关的成年对照组中得到了进一步证实。有趣的是，158Val 等位基因存在于表观遗传表型范围的两端，这与 COMT 单倍型对应表型变异性连续体的最近提出的模型一致。
我们的研究发现 S-COMT 启动子甲基化具有很强的遗传性，在未来研究 COMT 表型与表型之间的相互作用时需要考虑这一点。
