Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

Abstract

Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene-gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein b3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case-control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048-2.033, P ¼ 0.0255). In analysis of gene-gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (Po0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117-1.987, P ¼ 0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

“…3 As a result, RAS genes encoding for angiotensinogen (AGT), angiotensin type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE) have been widely investigated in different ethnic populations. [4][5][6][7][8] In addition, recent studies have shown that the promoter variants of AGT gene significantly influence the rate of AGT transcription and plasma AGT. 9,10 Conflicting or even contradictory reports have been seen regarding the association between RAS gene polymorphisms and EH incidence, of EH.…”

Variable selection in logistic regression for detecting SNP–SNP interactions: the rheumatoid arthritis example

“…The limitations of variable selection in LRs for testing SNP -SNP interactions have been widely discussed. 10,22,28,29 The primary limitation is the empty cell-effect that some genotype combinations have low frequency or zero responses. In an LR, two dummy parameters are usually needed for each SNP and more parameters are required for their interactions.…”

Hypertension and genes: perspectives from this journal

“…Recent studies conducted in relation to genetic susceptibility to hypertension suggest that the AGT gene has relatively more consistent positive associations. 1,3 For example, Nakamura et al reported that the M235T genetic variant of the AGT gene was associated with an increased risk of hypertension in Japanese population, 4 but this association is not always observed in other ethnic populations, such as Australian Anglo-Celtic Caucasians or black AfroCaribbeans. Studies carried out on the ACE I/D polymorphisms are also conflicting-some show gender-specific associations, while others show that the D allele significantly increases the risk of hypertension in men of European and Japanese origin.…”

“…Studies carried out on the ACE I/D polymorphisms are also conflicting-some show gender-specific associations, while others show that the D allele significantly increases the risk of hypertension in men of European and Japanese origin. 1,3 One pathway that has been associated with hypertension is the G-protein/signal transduction pathway system. Until recently, the C825T polymorphism in the b3-subunit of G-protein gene (GNB3) has been significantly linked with essential hypertension in Africans and Caucasians.…”

“…However, similar studies among Asians have presented conflicting results, perhaps due to the genetic and environmental heterogeneity among different ethnic backgrounds. Indeed, Bae et al 3 recently studied interactions between the GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans, and concluded that there was a significant interaction between the allelic variants GNB3 825T and ACE D, which may contribute to the genetic predisposition to essential hypertension in Koreans.…”