705: Maternal carriage of the K121Q single nucleotide polymorphism (SNP) in the ENPP (PC-1) gene is associated with preterm birth and diminished birthweight in a hispanic population

Abstract

THE ENPP (PC-1) GENE IS ASSOCIATED WITH PRETERM BIRTH AND DIMINISHED BIRTHWEIGHT IN A HISPANIC POPULATION ERROL NORWITZ, VICTORIA SNEGOVSKIKH, CHARLES LOCKWOOD, EDWARD KUCZYNSKI, LOUIS MUGLIA, DANIEL TILDEN, BETH KOZEL, EDMUND FUNAI, MERT O. BAHTIYAR, GUOYANG LUO, STEPHEN THUNG, THOMAS MORGAN, Yale University, New Haven, Connecticut, Washington University, St. Louis, Missouri OBJECTIVE: Preterm birth (PTB) is a major cause of perinatal mortality and morbidity. Familial clustering, racial disparities, and the high incidence of recurrent PTB suggest that maternal genetic factors are involved. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), also known as plasma cell glycoprotein-1 (PC-1), is a surface protein involved in cell differentiation and calcium transport. The K121Q(A C) SNP of this gene is associated with arterial calcification syndromes, insulin resistance, type-2 diabetes, and obesity. This study investigates for the first time the association between the K121Q SNP in the maternal ENPP1 gene and PTB. STUDY DESIGN: Patients with spontaneous PTB were identified at Yale, NYU, and Wash U. Controls were term deliveries. DNA was extracted from stored buffy coats and genotyped for the ENPP1 SNP using established primers and the Sequenom MALDI-TOF platform. All specimens were linked with medical data abstrated from maternal/neonatal records. Data were analyzed by chi-square tests and logistic regression analysis. The analysis was confined to Hispanics due to lack of power for other ethnic groups. RESULTS: Genotyping was successful in 99.4% of samples. ENPP1 CC genotype was present in higher frequency in PTB cases (19.7% [14/71]) vs controls (7.1% [15/211]; p 0.0004). The C allele frequency was 0.39 in cases and 0.21 in controls. There was no deviation from Hardy-Weinberg expectations in cases (p 0.14), but there was a slight excess of heterozygotes (n 11) among controls (p 0.02). There was a significant linear trend towards decreasing birthweight with increasing number of C alleles (ANOVA F 10.3; p 0.002), and the association between PTB and ENPP1 genotype remained significant after adjusting for birthweight (p 0.048). CONCLUSION: The K121Q (CC) genotype in the maternal ENPP1 gene is independently associated with PTB, and there is a linear trend towards diminished birthweight with increasing exposure to the C allele. Larger studies of PTB are needed to confirm these observations. Funded by March of Dimes #21-FY05-1250 (to E.N.).