title: Differential Association of Niemann-Pick C1 Gene Polymorphisms with Maternal Prepregnancy Overweight and Gestational Diabetes.
abstract: A genome-wide association study (GWAS) and subsequent replication studies in diverse ethnic groups indicate that common Niemann-Pick C1 gene (NPC1) polymorphisms are associated with morbid-adult obesity or diabetes independent of body weight. The objectives for this prospective cross-sectional study were to determine allele frequencies forNPC1polymorphisms (644A>G, 1926C>G, 2572A>G, and 3797G>A) and association with metabolic disease phenotypes in an ethnically diverse New Mexican obstetric population. Allele frequencies for 1926C>G, 2572A>G, and 3797G>A were significantly different between race/ethnic groups (non-Hispanic white, Hispanic, and Native American). The results also indicated a significant pairwise linkage-disequilibrium between each of the fourNPC1polymorphisms in race/ethnic groups. Moreover, the derived and major allele for 1926C>G was associated (OR 2.11, 95% CI 1.10-3.96, P = 0.022) with increased risk for maternal prepregnancy overweight (BMI 25.0-29.9kg/m2) while the ancestral and major allele for 2572A>G was associated (OR 4.68, 95% CI 1.23-17.8, P = 0.024) with increased risk for gestational diabetes in non-Hispanic whites, but not Hispanics or Native Americans. In summary, this is the first transferability study to investigate commonNPC1polymorphisms in a multiethnic population and demonstrate a differential association with increased risk for maternal prepregnancy overweight and gestational diabetes.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Garver
authors.affiliation: Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Lesley
authors.initials: L
authors.lastname: de la Torre
authors.affiliation: Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Brennan
authors.affiliation: Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jelinek
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Castillo
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Orlando
authors.affiliation: Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Randall A
authors.initials: RA
authors.lastname: Heidenreich
authors.affiliation: Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Rayburn
keywords: Gestational diabetes; Niemann-Pick C1; Obesity; Obstetrics; Overweight; Polymorphism