Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.
Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.
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人儿茶酚-O-甲基转移酶基因的低酶活性单倍型：标记SNP的富集。
DOI：
10.1371/journal.pone.0005237
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Diatchenko L
中科院分区：
文献类型：
--
作者：
Nackley AG;Shabalina SA;Lambert JE;Conrad MS;Gibson DG;Spiridonov AN;Satterfield SK;Diatchenko L
Catechol-O-methyltransferase (COMT) is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val 158 met) position, designated as low (LPS), average (APS), and high pain sensitive (HPS), are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs), accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224) is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488) are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.
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影响因子：
3.5
作者：
Diatchenko, L;Slade, GD;Maixner, W
通讯作者：
Maixner, W
DOI：
10.1002/ajmg.b.30649
发表时间：
2008-07-05
影响因子：
2.8
作者：
Hong, Jin Pyo;Lee, Joongsun S.;Kim, Chang Yoon
通讯作者：
Kim, Chang Yoon
DOI：
10.1017/s146114570400416x
发表时间：
2004-06-01
影响因子：
4.8
作者：
Domschke, K;Freitag, CM;Deckert, J
通讯作者：
Deckert, J
影响因子：
30.8
作者：
Kern, AD;Kondrashov, FA
通讯作者：
Kondrashov, FA
DOI：
10.1073/pnas.92.20.9047
发表时间：
1995-09-26
影响因子：
11.1
作者：
KIRBY, DA;MUSE, SV;STEPHAN, W
通讯作者：
STEPHAN, W