Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome.
Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome.
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DOI：
10.1001/jama.2013.3411
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发表时间：
2013-05-01
影响因子：
120.7
通讯作者：
Davis, Jonathan M.
中科院分区：
文献类型：
--
作者：
Wachman, Elisha M.;Hayes, Marie J.;Brown, Mark S.;Paul, Jonathan;Harvey-Wilkes, Karen;Terrin, Norma;Huggins, Gordon S.;Aranda, Jacob V.;Davis, Jonathan M.
新生儿戒断综合征（NAS）引起的子宫内阿片类药物暴露是一个日益严重的问题；影响发病率和严重程度的遗传因素以前没有研究过。μ-阿片受体（OPRM1）、多药耐药（ABCB1）和儿茶酚-o-甲基转移酶（COMT）基因的单核苷酸多态性（snp）与成人阿片成瘾风险相关。确定OPRM1、ABCB1和COMT基因的snp是否与住院时间和NAS治疗需求相关。2011年7月至2012年7月在马萨诸塞州和缅因州的5个三级保健中心和社区医院进行的前瞻性多中心队列研究。DNA样本的snp基因分型，然后NAS结果与基因型相关。140对符合条件的母婴中有86对被纳入研究。如果婴儿的胎龄在36周或更大，并且在子宫内暴露于美沙酮或丁丙诺啡，则符合条件。主要结局指标为住院时间，组间差异用β表示，用线性回归模型计算。次要结局指标包括NAS是否需要任何药物治疗以及是否需要两种或两种以上药物治疗。具有OPRM1 118A>G AG/GG基因型的婴儿住院时间缩短（β = - 8.5天；95% CI, - 14.9至- 2.1天；P = 0.009），接受任何治疗的可能性低于AA婴儿（48% vs 72%；调整优势比，0.76;95% CI, 0.63-0.96; P = 0.006）。COMT 158A>G AG/GG基因型与缩短住院时间（β = - 10.8天；95% CI, - 18.2至- 3.4天；P = 0.005）和减少2种或更多药物的治疗（18% vs 56%；调整优势比，0.68;95% CI, 0.55-0.86; P = 0.001）相关。与ABCB1 snp的相关性不显著。在NAS患儿中，OPRM1和COMT基因的变异与较短的住院时间和较少的治疗需求相关。这些初步发现可能为NAS的潜在机制提供见解。
Neonatal abstinence syndrome (NAS) caused by in utero opioid exposure is a growing problem; genetic factors influencing the incidence and severity have not been previously examined. Single-nucleotide polymorphisms (SNPs) in the μ-opioid receptor (OPRM1), multidrug resistance (ABCB1), and catechol-o-methyltransferase (COMT) genes are associated with risk for opioid addiction in adults. To determine whether SNPs in the OPRM1, ABCB1, and COMT genes are associated with length of hospital stay and the need for treatment of NAS. Prospective multicenter cohort study conducted at 5 tertiary care centers and community hospitals in Massachusetts and Maine between July 2011 and July 2012. DNA samples were genotyped for SNPs, and then NAS outcomes were correlated with genotype. Eighty-six of 140 eligible mother-infant dyads were enrolled. Infants were eligible if they were 36 weeks’ gestational age or older and exposed to methadone or buprenorphine in utero. Primary outcome measure was length of hospital stay, with between-group differences expressed as β and calculated with linear regression models. Secondary outcome measures included need for any medical treatment for NAS and treatment with 2 or more medications. Infants with the OPRM1 118A>G AG/GG genotype had shortened length of stay (β = −8.5 days; 95% CI, −14.9 to −2.1 days; P = .009) and were less likely to receive any treatment than AA infants (48% vs 72%; adjusted odds ratio, 0.76; 95% CI, 0.63–0.96; P = .006). The COMT 158A>G AG/GG genotype was associated with shortened length of stay (β = −10.8 days; 95% CI, −18.2 to −3.4 days; P = .005) and less treatment with 2 or more medications (18% vs 56%; adjusted odds ratio, 0.68; 95% CI, 0.55–0.86; P = .001) than the AA genotype. Associations with the ABCB1 SNPs were not significant. Among infants with NAS, variants in the OPRM1 and COMT genes were associated with a shorter length of hospital stay and less need for treatment. These preliminary findings may provide insight into the mechanisms underlying NAS.
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DOI：
10.1073/pnas.1018699108
发表时间：
2011-05-31
影响因子：
11.1
作者：
Ray, Riju;Ruparel, Kosha;Lerman, Caryn
通讯作者：
Lerman, Caryn
影响因子：
3.5
作者：
Levran, Orna;O'Hara, Kimberly;Kreek, Mary Jeanne
通讯作者：
Kreek, Mary Jeanne
影响因子：
120.7
作者：
Patrick, Stephen W.;Schumacher, Robert E.;Davis, Matthew M.
通讯作者：
Davis, Matthew M.
影响因子：
7.4
作者：
Rakvåg, TT;Klepstad, P;Skorpen, F
通讯作者：
Skorpen, F
影响因子：
7.4
作者：
Reyes-Gibby, Cielito C.;Shete, Sanjay;Klepstad, Pål
通讯作者：
Klepstad, Pål