AGTR2 gene variant predicts risk for preeclampsia

Carriers of a variant of the angiotensin II receptor, type 2 (AGTR2) gene have increased risk for preeclampsia during pregnancy if they are also overweight or obese, show study results published in Placenta.

"Understanding this association could help to predict which women are likely to develop preeclampsia," commented senior investigator Claire Roberts (University of Adelaide, Australia) in a press statement.

"However, it also helps to reinforce the message that a normal weight prior to pregnancy will lower the risk of serious complications - being overweight or obese increases the risk of complications."

The researchers recruited 2121 Caucasian couples and their babies to take part in the Screening for Pregnancy Endpoints (SCOPE) study in Adelaide, Australia. Of the pregnancies, 123 were preeclamptic and 1185 were uncomplicated.

All the parent-child trios were genotyped for four single nucleotide polymorphisms (SNPs) in the AGTR2 (C4599A, A1675G, and T1134C) and AGTR1 (A1166C) genes on the X-chromosome.

An association was found between the AGTR2 SNP C4599A (rs11091046) and preeclampsia, although it was not statistically significant in the cohort overall.

However, when the body mass index (BMI) of the mothers was taken into account, there was a significant 2.1-fold increased risk for preeclampsia for mothers with a BMI of 25 kg/m2 or above (overweight) if they had the AA genotype for C4599A, relative to those with the CC genotype.

If neonates were A allele carriers for C4599A (AA or AC genotypes if female, and A if male) and their mothers were overweight it increased the mother's risk for experiencing preeclampsia 3.5-fold.

Similarly, the partners of fathers who were A-allele carriers for this SNP also had a significant 1.9-fold increased risk for preeclampsia and uterine bilateral notching at 20 weeks' gestation, a risk factor for preeclampsia, if they were overweight.

"This is a condition that can run in families," said Roberts. "With both the mother and the father passing on their variant genes to their children, this places the child at greater risk of parenting a pre-eclamptic pregnancy."

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