Functional maternal catechol-O-methyltransferase polymorphism and fetal growth restriction
Functional maternal catechol-O-methyltransferase polymorphism and fetal growth restriction
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功能性母体儿茶酚-O-甲基转移酶多态性与胎儿生长受限
DOI：
10.1097/01.fpc.0000230116.49452.c0
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发表时间：
2006
影响因子：
2.6
通讯作者：
R. Kishi
中科院分区：
文献类型：
--
作者：
F. Sata;Hideto Yamada;Kana Suzuki;Y. Saijo;T. Yamada;H. Minakami;R. Kishi
目的胎儿宫内生长受限发生在细胞和分子水平的病理生理过程在很大程度上尚不清楚。儿茶酚-O-甲基转移酶(COMT)是一种通过甲基转移使儿茶酚雌激素失活的II相酶。COMT基因的功能性Val158Met多态已被认为是乳腺癌的易感标志物。本研究的目的是研究该基因多态与胎儿生长发育之间的关系。方法在出生队列研究中，对连续412名经历过单胎分娩的妇女进行评估。COMT和CYP17A1基因多态的基因分型采用荧光探针等位基因识别和5‘端核酸酶分析。结果低活动纯合子(COMT-L)纯合子妇女发生低出生体重风险的调整优势比(<；2.500 g)为2.98(95%可信区间为1.10~8.11)。母亲为COMT-L纯合子的新生儿平均出生体重低于母亲至少有一个高活性(COMT-H)等位基因的新生儿(2.610 g对2.800 pg，P=0.07)。在COMT-L等位基因纯合子妇女中，胎儿宫内生长受限风险的优势比为2.63/2.57(95%可信区间为1.14~6.05/0.96~6.88)。在隐性基因模型中，COMT-L纯合子发生低出生体重和胎儿宫内发育受限的优势比分别为3.36(95%可信区间，1.30~8.65)和2.89/2.65(95%可信区间，1.31~6.34/1.06~6.65)。出生体重与纯合子细胞色素P17A1 A2基因呈正相关(P<；0.01)。当同时考虑COMT和CYP17A1基因型时，发现COMT-L和CYP17A1纯合子妇女发生低出生体重/胎儿宫内生长受限的风险最高。在这些妇女中，胎儿宫内发育受限风险的优势比(<；10%)为5.35(95%可信区间，1.15-25.0)。结论编码低活性COMT的等位基因可能是胎儿宫内生长受限的易感标志。
Objectives The pathophysiologic processes that occur at the cellular and molecular levels in intrauterine fetal growth restriction are largely unknown. Catechol-O-methyltransferase (COMT) is a phase II enzyme that inactivates catechol estrogens by transfer of a methyl group. A functional Val158Met polymorphism in the COMT gene has been known as a susceptible marker for breast cancer. The aim of this study was to examine the association between this polymorphism and fetal growth. Methods A consecutive series of 412 women who experienced singleton deliveries was assessed in the birth cohort study. Genotyping of COMT and CYP17A1 polymorphisms was determined by allelic discrimination using fluorogenic probes and the 5′nuclease assay. Results The adjusted odds ratio for the risk of low birth weight (<2.500 g) in women with homozygous low-activity (COMT-L) alleles was 2.98 (95% confidence interval, 1.10–8.11). The mean birth weight of infants whose mothers were homozygous for COMT-L was less than that of infants whose mothers had at least one high-activity (COMT-H) allele (2.610 versus 2.800 g, P=0.07). The odds ratio for the risk of intrauterine fetal growth restriction, defined as birth weight <10th percentile or <mean–1.5 SD, in women homozygous for COMT-L alleles was 2.63/2.57 (95% confidence interval, 1.14–6.05/0.96–6.88). In the recessive genotype model, the odds ratios for the risk of low birth weight and intrauterine fetal growth restriction in women homozygous for COMT-L were 3.36 (95% confidence interval, 1.30–8.65) and 2.89/2.65 (95% confidence interval, 1.31–6.34/1.06–6.65), respectively. A positive association exists between birth weight and the homozygous CYP17A1 A2 genotype (P<0.01). When both COMT and CYP17A1 genotypes were considered, the highest risk of low birth weight/intrauterine fetal growth restriction was found among women with the homozygous COMT-L and CYP17A1 A1 genotype. The odds ratio for the risk of intrauterine fetal growth restriction (<10th percentile) in those women was 5.35 (95% confidence interval, 1.15–25.0). Conclusion Our findings suggest that the allele encoding low-activity COMT may be a susceptible marker for intrauterine fetal growth restriction.
编码儿茶酚-O-甲基转移酶低活性变体的等位基因与乳腺癌风险之间的关联。
影响因子：
11.2
作者：
Lavigne,JA;Helzlsouer,KJ;Huang,HY;Strickland,PT;Bell,DA;Selmin,O;Watson,MA;Hoffman,S;Comstock,GW;Yager,JD
通讯作者：
Yager,JD
DOI：
10.1097/00008571-199606000-00007
发表时间：
1996-06-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Lachman, HM;Papolos, DF;Weinshilboum, RM
通讯作者：
Weinshilboum, RM
影响因子：
11.2
作者：
H. Feigelson;G. Coetzee;L. Kolonel;R. Ross;B. Henderson
通讯作者：
H. Feigelson;G. Coetzee;L. Kolonel;R. Ross;B. Henderson