This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.A.
Specific Aims :The original goal of this study was to study the genetic susectibility to placental complications of prenatal methamphetamine use. The pilot study was to do a candidate gene study on methamphetamine users, smokers, and healthy controls, looking at polymorphisms of the norepinephrine and serotonin transporter genes. Interestingly the drug users did not differ in their genotype or allele frequencies from the controls, but the smokers did. This led me to expand my area of study to look at both smoking and methamphetamine use effects on the placenta and the genetic links to addiction. To this end, I have expanded specific aim #1 and added specific aim #2. In addition, the Perinatal Addiction Treatment of Hawaii (PATH) clinic has continued expansion, and we have had over 21 deliveries of moms with documented drug use during pregnancy, along with the specific timing of exposure, pregnancy outcomes and complication data. To this end, I have developed specific aim #3 so that this data, along with genotype information will be available for future researchers.
Specific Aim 1 : The Placental Effects of Methamphetamines and Tobacco: In this study, placentas from users of methamphetamines are gathered after delivery and compared with control placentas, both smokers and non-smokers. Pregnancy outcomes from these women are being tracked, noting the occurrence of preeclampsia, abruption, preterm labor, and intrauterine growth restriction. Cord segments will be analyzed for the five main substance of abuse (methamphetamine, amphetamine, marijuana, opiates, and cocaine) to confirm drug use, rule out confounding effects from multiple drug exposure and correlate with the placental findings.
Specific Aim 2 : The genetic polymorphisms associated with persistent smoking during pregnancy. Our preliminary studies have shown an association of two single nucleotide polymorphisms (SNPs) of the norepinephrine gene with persistent smoking during pregnancy. Through the PRCEHD core lab, we are currently collecting DNA from smokers and control women of various ethnicities to establish baseline allele frequencies in our population and to confirm this association. We will also perform genotyping of two of the most commonly studied serotonin polymorphisms, the 5HTT gene-linked polymorphic region (5HTTLPR) and the variable length tandem repeat (VNTR) in intron 2, as well as the SNPs (rs1051730 and rs8034191) seen in Amos et al study linking nicotinic acetylcholine receptors with lung cancer risk in smokers. This will be a novel way to see if this receptor is also linked with the complications with smoking during pregnancy. We will be doing cotine levels on the women's blood at delivery to confirm their smoking status, which will strengthen the association and remove recall bias inherent in self-reported smoking status.
Specific Aim 3 : Establish a clinical and DNA database on pregnant substance-using patients. The Perinatal Addiction Treatment of Hawaii (PATH) clinic was established in 2007. Since that time we have cared for over 75 women with addictions, mostly to methamphetamines. We have documented last use and toxicology data, as well as pregnancy and birth outcomes for the 22 of these women who have delivered. This information will be collected in a database along with DNA samples of the mother, similar to the database established by the Pacific Research Center for Early Human Development (PRCEHD) database. This will allow us to study the genetic factors leading to addiction, the pregnancy complications from methamphetamine use, and the programmatic components that best influence successful recovery.
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