Genetic Variants, Endothelial Function, and Risk of Preeclampsia Among American Indians

Abstract

Objective. To determine the prevalence in an American Indian population of genetic variants with putative effects on endothelial function and determine whether they are associated with preeclampsia. Methods. Five genetic polymorphisms potentially related to endothelial function in the NOS3, GNB3, and DDAH1 genes were genotyped from a total of 101 cases, 198 controls, and an additional 110 population-based controls among an American Indian population. Results. The minor allele frequencies for NOS3 (rs1799983, rs3918227), GNB3 (rs5442), and DDAH1 (rs10158674, rs233115) among those with and without PE in this population were 25, 10, 5, 11, and 30%, respectively. Although not statistically significant, the maximum risk associated with any of these SNPs was 2.22 (0.734–6.73, 95% CI, p = 0.156) in a multivariate analysis of the A allele of the rs233115 SNP incorporated in a recessive model. Conclusion. Although endothelial dysfunction likely plays a role in the pathophysiology of PE, this study was unable to find evidence for an association between these five SNPs on three genes influencing endothelial function and PE. This may be due to insufficient power to detect an association, investigation of SNPs without linkage to risk of PE in this population or other factors. Investigation of additional SNPs in these or related genes and other populations seems warranted.

• American Indian
• Endothelial dysfunction
• Genetics
• Preeclampsia

ACKNOWLEDGEMENTS

We thank the study participants, IHS facilities, and participating tribal communities for their extraordinary cooperation and involvement, which has been critical to the success of this investigation. Assistance in identifying and obtaining control material and genotypes from Dr. Guillaume Pare, McMaster University, Hamilton, Ontario, is gratefully recognized. This publication was made possible by NIH Grant Number P20 RR016741 (INBRE) from the National Center for Research Resources (NCRR), and Grant Number W911NF-09-1-0016 from the Department of Defense. The views expressed in this paper are those of the authors and do not necessarily reflect those of the Indian Health Service, NCRR, or NIH.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.