TY - JOUR
T1 - The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia
AU - Thomsen, Liv Cecilie V.
AU - McCarthy, Nina S.
AU - Melton, Phillip E
AU - Cadby, Gemma
AU - Austgulen, Rigmor
AU - Nygard, Ottar K.
AU - Johnson, Matthew P.
AU - Brennecke, Shaun
AU - Moses, Eric K.
AU - Bjorge, Line
AU - Iversen, Ann-Charlotte
PY - 2017/1
Y1 - 2017/1
N2 - Objective: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia. Methods: We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genomewide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model. Results: The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53-0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case-control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83-1.32, minor allele frequency = 0.15). Conclusion: MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.
AB - Objective: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia. Methods: We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genomewide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model. Results: The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53-0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case-control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83-1.32, minor allele frequency = 0.15). Conclusion: MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.
KW - Blood pressure regulation
KW - Hypertension
KW - Methylenetetrahydrofolate reductase
KW - Pleiotropy
KW - Preeclampsia
KW - Single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=84991628482&partnerID=8YFLogxK
U2 - 10.1097/HJH.0000000000001131
DO - 10.1097/HJH.0000000000001131
M3 - Article
AN - SCOPUS:84991628482
SN - 0263-6352
VL - 35
SP - 132
EP - 139
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 1
ER -
