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Int J Mol Epidemiol Genet 2011;2(3):196-206

Original Article
A fetal variant in the GCM1 gene is associated with pregnancy induced
hypertension in a predominantly hispanic population

Melissa L. Wilson, Doerthe Brueggmann, Daniel H. Desmond, John E. Mandeville, T. Murphy Goodwin, Sue Ann Ingles

Department of Obstetrics and Gynecology, University of Southern California, Keck School of Medicine; Department of Preventive
Medicine, University of Southern California, Keck School of Medicine; Justus-Liebig-Universität, University Hospital Geissen
and Marburg, Klinikstrasse 32, 35385

Received March 7, 2011; accepted April 25, 2011; Epub May 5, 2010; published August 30, 2011

Abstract: The aim of the study was to determine whether polymorphism in the GCM1 gene is associated with pregnancy
induced hypertension (PIH) in a case-control study of mother-baby dyads. Predominantly Hispanic women, ages 15-45, with
(n=136) and without (n=169) PIH were recruited. We genotyped four polymorphisms in the GCM1 gene and examined the
association with PIH using both logistic regression and likelihood expectation maximization (LEM) to adjust for intra-familial
correlation between genotypes. Maternal genotype was not associated with PIH for any polymorphisms examined. Fetal
genotype, however, was associated with maternal risk of PIH. Mothers carrying a fetus with ≥1 copy of the minor (C) allele for
rs9349655 were less likely to develop PIH than women carrying a fetus with the GG genotype (parity-adjusted OR=0.44, 95%
CI: 0.21, 0.94). The trend of decreasing risk with increasing C alleles was also statistically significant (ORtrend=0.41 95% CI:
0.20, 0.85). The minor alleles for the other three SNPs also appear to be associated with protection. Multilocus analyses of fetal
genotypes showed that the protective effect of carrying minor alleles at rs9349655 and rs13200319 (non-significant) remained
unchanged when adjusting for genotypes at the other loci. However, the apparent (non-significant) effect of rs2816345 and
rs2518573 disappeared when adjusting for rs9349655. In conclusion, we found that a fetal GCM1 polymorphism is
significantly associated with PIH in a predominantly Hispanic population. These results suggest that GCM1 may represent a
fetal-effect gene, where risk to the mother is conferred only through carriage by the fetus. (IJMEG1103001).

Keywords: GCM1, preeclampsia, hypertension, pregnancy, genetics

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Address all correspondence to:
Dr. Melissa Wilson
#211 IRD
2020 Zonal Ave.
Los Angeles, CA 90033
Phone: 323-226-3306; Fax: 323-226-3509
melisslw@usc.edu