Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension

Abstract

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.

Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin–Angiotensin–Aldosterone System and Blood Pressure

“…Indeed, it has been argued that simply modeling genetic polymorphisms as independent and additive effects on the phenotype is not a realistic biological model and that epistasis should be included, 14 although others have questioned the relative importance of epistasis in complex traits. 15 Many studies have tested for epistasis in relation to polymorphisms of RAAS genes and have suggested interactions between AGT and ACE, 9,[16][17][18] between multiple genes, 19 and within haplotypes comprised of certain combinations of variants within individual genes. [20][21][22][23][24] Other studies have been unable to identify evidence that might indicate epistasis.…”

“…These 104 markers captured 262 validated SNPs with minor allele frequencies of >1%. They comprised 17 SNPs for REN (with rs11240688 tagging the commonly genotyped -5312C/T polymorphism at r 2 =1 according to the SNAP database, www.broadinstitute.org/mpg/snap/ldsearch.php), 16 for ACE (with rs4353 tagging the I/D polymorphism 34 ), 29 for AGT (with rs6687360 tagging the M235T polymorphism, r 2 =0.83), 33 for AGTR1 (with rs5186 as the A1166C polymorphism), and 9 for CYP11B2 (with rs1799998 tagging the −344C/T polymorphism, r 2 =0.90). These 104 tagSNPs, plus an additional 3 duplicate SNPs (included to test the reliability of the genotyping platform and check for concordance in genotype call), were processed by Sequenom MassARRAY Assay Design software v3.1 (Sequenom).…”

“…Many studies have tested for epistasis in relation to polymorphisms of RAAS genes and have suggested interactions between AGT and ACE, 9,[16][17][18] between multiple genes, 19 and within haplotypes comprised of certain combinations of variants within individual genes. [20][21][22][23][24] Other studies have been unable to identify evidence that might indicate epistasis.…”

Genetic polymorphisms in the angiotensin converting enzyme, actinin 3 and paraoxonase 1 genes in women with diabetes and hypertension

“…NCDs are associated to increased blood pressure, dyslipidemia and insulin resistance ( 6 ). Peripheral vascular resistance is regulated by angiotensin II and bradykinin; therefore, individuals with the DD genotype for the angiotensin converting enzyme (ACE) gene have increased blood pressure, while further studies are necessary to understand the role of this polymorphism in the development of NCDs ( 2 , 3 ). On the other hand, paraoxonase 1 (PON1) is an enzyme synthesized by the liver ( 4 ), with a role in protecting the low-density lipoprotein (LDL) against oxidative changes ( 5 ).…”

“…It originates from the imbalance between food consumption and energetic expenditure, and is influenced by physiological, genetic and behavioral aspects (1). Worldwide, it is estimated that 38.9% of adults 18 years or older have overweight and 13.1% have obesity, and both prevalence are higher in women (2)(3)(4).…”