Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy

Hocher, Berthold; Yp, Chen; Hügle, Sophia; Repey, Jenny; Krause, K; Slowinski, Torsten; Godes, Michael; Schaeffeler, Elke; Guthmann, Florian; Wauer, Roland R.; Halle, H; Gossing, Gabriele; Pfab, Thiemo

doi:10.1038/jhh.2008.34

Cited by 13 publications

(6 citation statements)

References 45 publications

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“…Others, however, have found no association between this polymorphism and PE. 16 Several studies have measured circulating NO levels in PE and found them to be decreased, 17 increased 5,18 or unchanged. 19 We did not find any significant differences in the total circulating NO levels in any of the groups.…”

Section: Discussionmentioning

confidence: 99%

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

2010

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We investigated the variations in genes encoding endothelial nitric oxide synthase (NOS3), angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) in hypertensive disorders of pregnancy and the relationship between the polymorphisms and circulating nitric oxide (NO) and ACE levels in pregnant north Indian women. Frequencies of NOS3 G894T, 4b/a and T -786 -C, AGT T704C and ACE ins/del polymorphisms were studied in 342 subjects: 120 with preeclampsia (PE), 104 with gestational hypertension and 118 normotensive pregnant women. Variations were evaluated by polymerase chain reactionrestriction fragment length polymorphism. NO and ACE levels were determined using ELISA. There was no difference in the distribution of individual NOS3 and ACE polymorphisms in the study groups. Haplotype analysis showed a global difference in the NOS3 haplotype distribution between the PE and non-PE subjects (P¼0.03). The presence of AGT 704C allele was associated with a reduced risk of developing PE (odds ratio: 0.33, 95% CI: 0.19-0.59 in recessive mode). Circulating total NO and ACE levels were similar in three groups. No relationship was found between circulating NO levels and any of the NOS3 polymorphisms, but the circulating ACE levels were higher in those with DD genotype (Po0.05). In conclusion, there was no association between individual NOS3 and the ACE gene polymorphisms and hypertensive disorders of pregnancy in north Indian women. The presence of minor alleles at all the three sites in NOS3 seemed to increase the risk of PE, and AGT 704C allele was associated with a reduced PE risk. The complexity of interaction between these genetic abnormalities requires further studies.

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Section: Discussionmentioning

confidence: 99%

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

2010

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“…Of those, 15 were excluded, 7 did not include sufficient data (Matsubara et al, 2001;Savvidou et al, 2001;Hingorani, 2003;Yu et al, 2003;Donker et al, 2005;Corthorn et al, 2006;Barut et al, 2010;Best et al, 2010), 4 were not published in English (Tong et al, 1998;Zhou et al, 1998Zhou et al, , 2003Kukor and Valent, 2010), 2 were letters (Moreno, 2008;Seremak-Mrozikiewicz et al, 2008), 1 did not include control group (Hocher et al, 2008), 1 was a review (Hingorani, 2003), and 25 were considered eligible for the metaanalysis. Of those, seven studies were excluded (Kobashi et al, 2001;Grandone et al, 2003;Tempfer et al, 2004;Chen et al, 2007;Nishizawa et al, 2009;Singh et al, 2010;Sharma et al, 2011), because the distribution of the genotypes in the control group was not in HWE ( p < 0.05).…”

Section: Study Selectionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Gene Polymorphisms (G894T, 4b/a and T-786C) and Preeclampsia: Meta-Analysis of 18 Case–Control Studies

Chen

Zhao

Sun

et al. 2012

DNA and Cell Biology

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Studies investigating the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and preeclampsia reported contradictory or nonconclusive results. We performed a meta-analysis of 18 genetic association studies that examined the relationship between preeclampsia and the G894T, 4a/b and T-786C polymorphisms of the eNOS gene. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The MEDLINE, EMBASE, and Google Scholar databases were searched to access the relevant genetic association studies up to June 2011. For the allelic analysis of the G894T variant, all studies showed no significant association. For the genotypic analysis, the combined studies of the G allele showed negative significance (odds ratio [OR]=0.56; 95% confidence interval [CI]: 0.33-0.97), all the studies showed positively significance when the T allele was combined (OR=1.17; 95% CI: 1.01-1.36), and results were also positively significant in non-Asian populations (OR=1.20; 95% CI: 1.02-1.43). For the allelic analysis of the 4b/a variant, all studies showed no significant association, but results were negatively significant in non-Asian populations (OR=0.67; 95% CI: 0.46-0.98). For the genotype analysis, combined studies of the b allele showed negative significance (OR=0.55; 95% CI: 0.36-0.84). Moreover, non-Asian studies showed negatively significant results (OR=0.45; 95% CI: 0.28-0.72). For the analysis of the T-786C variant, none of the studies showed significant results. The synthesis of available evidence supports the fact that intron 4a allele, homozygosity for the 894T and intron 4a of eNOS are positively associated with preeclampsia. Large, multiethnic confirmatory, and well-designed studies are needed to determine the relation between preeclampsia and polymorphisms of the eNOS gene.

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“…Various genetic and environmental factors have been known that contribute in pathogenesis of this disorder [3]. Ward and Lindheimer reported an incident risk of 20 to 40 percent for daughters of preeclamptic mothers, 11 to 37 percent for sisters of preeclamptic women, and 22 to 47 percent in twin studies for preeclampsia [4].…”

Section: Introductionmentioning

confidence: 99%

Association of Angiotensin‐Converting Enzyme Intron 16 Insertion/Deletion and Angiotensin II Type 1 Receptor A1166C Gene Polymorphisms with Preeclampsia in South East of Iran

Salimi

Mokhtari²,

Yaghmaei³

et al. 2011

BioMed Research International

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Some evidence suggests that a variety of genetic factors contributed in pathogenesis of the preeclampsia. The aim of this study was to assess the association between the angiotensin-converting enzyme (ACE) I/D and angiotensin II type1 receptor A1166C polymorphisms with preeclampsia. This study was performed in 125 preeclamptic pregnant women and 132 controls. The I/D Polymorphism of the ACE gene was assessed by polymerase chain reaction and the A1166C Polymorphism of the AT1R gene was determined by restriction fragment length polymorphism. The genotype and allele frequencies of I/D polymorphism differed between two groups. The risk of preeclampsia was 3.2-fold in pregnant women with D allele (OR, 3.2 [95% CI, 1.1 to 3.8]; P = 0.01). The distribution of the AT1R gene A1166C polymorphism was similar in affected and control groups. Our results supported that presence of the I/D polymorphism of ACE gene is a marker for the increased risk of preeclampsia.

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Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy

Cited by 13 publications

References 45 publications

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

Endothelial Nitric Oxide Synthase Gene Polymorphisms (G894T, 4b/a and T-786C) and Preeclampsia: Meta-Analysis of 18 Case–Control Studies

Association of Angiotensin‐Converting Enzyme Intron 16 Insertion/Deletion and Angiotensin II Type 1 Receptor A1166C Gene Polymorphisms with Preeclampsia in South East of Iran

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