AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia.
The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A polymorphism with susceptibility to preeclampsia was studied in 252 women consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166 A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and 48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%, respectively). The presence of G allele was associated with 1.69-fold increased risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and diastolic blood pressures in the presence of GG+GA genotype were significantly higher compared to those in the presence of AA genotype. The concomitant presence of both alleles of AT2R G and AT1R C was associated with 1.3 times increased risk of mild preeclampsia (p=0.03). There was an interaction between AT2R G and ACE D alleles that significantly increased the risk of mild and severe preeclampsia by 1.38- and 1.3-fold, respectively. Also, interaction between MMP-9 T and AT2R G alleles increased the risk of severe preeclampsia 1.39-fold (p=0.028). Our study demonstrated that the G allele of AT2R -1332 G:A polymorphism is associated with an increased risk of preeclampsia. Also, epistatic interaction of G allele and each allele of the AT1R C, ACE D and MMP-9 T was associated with the risk of preeclampsia. Our findings suggest that the renin-angiotensin system (RAS) variants and gene-gene interactions affect the risk of preeclampsia.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: zrahimi@kums.ac.ir.
Zohreh
Z
Rahimi
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Ziba
Z
Rahimi
Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Amir
A
Aghaei
Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Asad
A
Vaisi-Raygani
D000328:Adult; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
ACE; AT1R; AT2R; MMP-9; Polymorphism; Preeclampsia