Single nucleotide polymorphisms and pregnancy complications

Federica Tarquini, Giuliana Coata, Elena Picchiassi, and Gian Carlo Di Renzo

Pregnancy induces significant maternal physiologic changes to accommodate the demands of the developing fetoplacental unit (1).

Some women experience health problems during pregnancy. These complications can involve the mother’s health, the fetus’s health, or both. Even women who were healthy before getting pregnant can experience complications. These complications may make the pregnancy a low-, medium-, or high-risk pregnancy.

Getting early and regular prenatal care can help decrease the risk for problems by enabling healthcare providers to prevent, diagnose, treat, or manage conditions before they become serious.

Some common complications of pregnancy include, but are not limited to, the following: high blood pressure, gestational diabetes mellitus (GDM), infections, preeclampsia, preterm birth (PTB), pregnancy loss/miscarriage, and stillbirth.

Several adaptations to pregnancy begin early, continue steadily from late first trimester to term, and rapidly shift postpartum. These alterations in physiology can have a profound effect on disease processes unrelated to pregnancy.

Available data suggest that pregnancy complications have a familial tendency (2,3). Although both maternal and paternal genotypes contribute to the genetic makeup of the fetus, previous studies have suggested a significant maternal but not a paternal effect (4).

The advent of genomics has brought a series of powerful new tools in predicting pregnancy complications. Although technologies such as proteomics and metabolomics show great promise, it is with genomics, the study of the genetic sequence that we inherit from our parents, that we have the most experience. Genetic variations in the sequence of about 3 billion nucleotide pairs that make up our DNA comes in many forms, but the most common differences between people are in the form of single-nucleotide polymorphisms (SNPs).

Genetic polymorphism is an existence of two or more different alleles in one locus in DNA, more often than it is expected, according to mutation frequency in a population. Both the mutation and polymorphism are a qualitative and/or quantitative change in the genetic material. SNPs are point mutations, like insertion, deletion, or substitution of one of the nucleotides in a coding or uncoding DNA sequence. These are single-letter nucleotide changes that occur in 1% or more of the population. There are 12–15 million of such variants that have been meticulously catalogued by the human genome project in the publicly available database called dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP). A wide range of methods of finding polymorphisms is now available, like a genome-wide association study (GWAS) or genome-wide linkage study (GWLS). One study reported the results of the GWAS in which, as the first, a risk locus for preeclampsia on chromosome 2q14, near the inhibin ß B (INHBB) gene was identified. In that study, researchers had successfully genotyped 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls with the usage of the Illumina OmniExpress-12 BeadChip (5).

SNPs can lead to defective or even overactive enzymes, transporters, and receptors (6).

Several studies have examined associations between genetic variants and pregnancy complications.

Preterm birth

Genetic factors are believed to play an important role in PTB, with estimated heritability varying from 13% to 40% (7,8). A number of candidate-gene studies of PTB have identified several candidate genetic variants (9–13

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