The Risk of Coronary Artery Disease Associated with Cigarette Smoking and Hypercholesterolemia Is Additionally Increased by the Presence of the AT 1 R Gene 1166C Allele

Cigarette smoking and hypercholesterolemia influence the renin-angiotensin system (RAS) functions, including increased RAS-mediated vasoconstriction, mitogenic signaling, and angiotensin II type 1 receptor (AT1R) expression. We have explored the interactions of the AT1R gene 1166 A>C polymorphism and traditional risk factors using an epidemiological approach. The study cohort included 341 subjects; 172 were patients with angiographically confirmed coronary artery disease (CAD) and 169 were blood donors. The 1166 A>C polymorphism was genotyped using the PCR-RFLP method. We found a synergy of the 1166C allele with cigarette smoking (synergy indices: SI = 1.41, SIM = 1.33), LDL cholesterol levels > or = 3 mmol/l (SI = 1.25, SIM = 1.19), and elevated total cholesterol (> or =5 mmol/l) levels (SI = 1.15, SIM = 1.13). In each case, the estimated CAD risk was greater than that predicted by assuming the additivity and multiplication of effects. We conclude that the 1166C allele increases the risk of CAD associated with the presence of cigarette smoking and hypercholesterolemia.     

Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease

Abstract

Association between angiotensin II type-1 receptor (AT1R) A1166C gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. This meta-analysis was performed to evaluate the association of AT1R A1166C gene polymorphism with ESRD susceptibility. The search was performed in the databases of PubMed, Embase and Cochrane Library as of 1 May 2012, and the eligible investigations were recruited for this meta-analysis. Nineteen literatures were identified for the analysis of association between AT1R A1166C gene polymorphism and ESRD susceptibility. There was no association between AT1R A1166C gene polymorphism and ESRD susceptibility for overall populations, Caucasians, Asians and Turkish population. Interestingly, CC genotype was associated with a higher risk of ESRD in Africans (OR?=?3.36, 95% CI: 1.42–7.99, p?=?0.006). However, C allele and AA genotype were not associated with the ESRD risk in African population. In conclusion, CC genotype might be a risk factor for the ESRD susceptibility in African population. However, more case-control association investigations on larger, stratified populations are required in the future.     

The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microrna-155 binding

The adverse effects of angiotensin II (Ang II) are primarily mediated through the Ang II type 1 receptor (AT1R). A silent polymorphism (+1166 A/C) in the human AT1R gene has been associated with cardiovascular disease, possibly as a result of enhanced AT(1)R activity. Because this polymorphism occurs in the 3'-untranslated region of the human AT1R gene, the biological importance of this mutation has always been questionable. Computer alignment demonstrated that the +1166 A/C polymorphism occurred in a cis-regulatory site, which is recognized by a specific microRNA (miRNA), miR-155. miRNAs are noncoding RNAs that silence gene expression by base-pairing with complementary sequences in the 3'-untranslated region of target RNAs. When the +1166 C-allele is present, base-pairing complementarity is interrupted, and the ability of miR-155 to interact with the cis-regulatory site is decreased. As a result, miR-155 no longer attenuates translation as efficiently as demonstrated by luciferase reporter and Ang II radioreceptor binding assays. In situ hybridization experiments demonstrated that mature miR-155 is abundantly expressed in the same cell types as the AT1R (e.g. endothelial and vascular smooth muscle). Finally, when human primary vascular smooth muscle cells were transfected with an antisense miR-155 inhibitor, endogenous human AT1R expression and Ang II-induced ERK1/2 activation were significantly increased. Taken together, our study demonstrates that the AT1R and miR-155 are co-expressed and that miR-155 translationally represses the expression of AT1R in vivo. Therefore, our study provides the first feasible biochemical mechanism by which the +1166 A/C polymorphism can lead to increased AT1R densities and possibly cardiovascular disease.     

ACE and AGTR1 genes polymorphisms in left ventricular hypertrophy pathogenesis in humans

The role of A2350G polymorphism in exon 17 of the ACE gene and A1166C - in 3'-UTR of the AGTR1 in the pathogenesis of left ventricular hypertrophy was studied in patients with essential hypertension (EH) and arterial hypertension combined with diabetes mellitus type 2 (AH + DM2). Patients with EH and AH + DM2 did not differ from the control sample of healthy individuals by allele or genotype frequencies. However, an association of both polymorphisms with LVH was detected in EH patients. The frequency of 1166C allele was higher in patients with LVH (33.6% vs 20.7% without LVH). A1166C polymorphism determined the magnitude of left ventricular mass index (LVMI) in EH patients as well (p = 0.007). 2350G allele frequency of the ACE gene was in 1.5, and GG genotype--in 3.5-fold higher in EH patients with LVH, as compared without LVH. LVMI was significantly higher in patients with GG genotype as compared with heterozygotes and AA homozygotes (p = 0.002). Thus the presence of 1166C allele of AGTR1 and 2350G allele of ACE can be considered as predisposing factors for LVH development in EH. In contrast, association of studied polymorphisms with presence or LVH degree was not detected in patients with arterial hypertension combined with DM2. This may indicate another structure of genetic component of predisposition to LVH in different causes.     

Association of polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 with ischemic chronic heart failure in the Russian and Tatar populations of Bashkortostan Republic

Polymerase chain reaction was used to study the association of polymorphic markers I/D of the angiotensin-converting enzyme gene (ACE) and A1166C of the angiotensin II type 1 receptor gene (AT2R1) with chronic heart failure (CHF) in Russian and Tatar patients that had had myocardial infarction. In Russian patients aged 50 years or younger that had had macrofocal myocardial infarction, the CC genotype of the A1166C polymorphic marker of gene AT2R1 was associated with an increased risk of CHF (OR = 11.36). Genotype DD and allele D of the I/D polymorphic marker of gene ACE were associated with a more severe CHF (functional class III-IV) in Russian patients (OR = 3.50 and 2.06). In Tatar patients, polymorphic markers I/D of gene ACE and A1166C of gene AT2R1 were not associated with CHF.     

Polymorphism of the angiotensin II type 1 receptor in patients with essential hypertension in Ukrainian population

The distribution of polymorphism of the angiotensin II type 1 receptor in Ukrainian population was investigated. Healthy persons had genotypes AA (51%), AC (34%), CC (15%) and alleles A (68%), C (32%). We suppose the prevalence of allele C and genotypes CC in health persons in Ukrainian population. The frequencies of genotypes and alleles in patients with essential hypertension were AA (22,85%), AC (51,9%), CC (25,3%) and A (48,7%), C (51,3%). Thus the development of essential hypertension was associated with the presence of allele C and its homozygote variant. Moreover the severity and complications of hypertension depended on the presence of this allele and genotype. We concluded that Ukrainian population has specific distribution of polymorphism of the angiotensin II type 1 receptor with prevalence of allele C1166 and genotype CC. The presence of these genetic variants is a risk factor for essential hypertension.     

Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes

Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally supported human miRNA targets. Of the 143 experimentally supported human target sites, 9 contain 12 SNPs. We further experimentally investigated one of these target sites for hsa-miR-155, within the 3' UTR of the human AGTR1 gene that contains SNP rs5186. Using reporter silencing assays, we show that hsa-miR-155 down-regulates the expression of only the 1166A, and not the 1166C, allele of rs5186. Remarkably, the 1166C allele has been associated with hypertension in many studies. Thus, the 1166C allele may be functionally associated with hypertension by abrogating regulation by hsa-miR-155, thereby elevating AGTR1 levels. Since hsa-miR-155 is on chromosome 21, we hypothesize that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of hsa-miR-155 leading to allele-specific underexpression of AGTR1. Indeed, we have shown in fibroblasts from monozygotic twins discordant for trisomy 21 that levels of AGTR1 protein are lower in trisomy 21.     

Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities,Nigeria

OBJECTIVES:

The angiotensin II protein is a vasoconstrictor that exerts most of its influence through the angiotensin II type 1 receptor (AT₁R). Inconsistent association between the A1166C polymorphism of the AT₁R gene and hypertension has been reported among various populations but not among the peoples of Calabar and Uyo. This study was designed to determine the frequency of the A1166C polymorphism of the AT₁R gene and its association with hypertension in a sample population of Calabar and Uyo.

MATERIALS AND METHODS:

A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls were randomly recruited from hypertension clinics and the general population. Genotyping of the A1166C allele of the AT₁R gene to identify variants was performed using polymerase chain reaction and restriction enzyme digestion. Multiple regressions were applied to test whether the A1166 genotypes were predictors of hypertension.

RESULTS:

99% of the study population had the wild type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism.

CONCLUSION:

The A1166C polymorphism was not a predictor of hypertension in the sample population of Calabar and Uyo.     

Frequency of angiotensin II type 1 receptor gene polymorphism in Turkish acute stroke patients

This study was performed in acute stroke patients in the Turkish population to determine the frequency of the A1166C polymorphism in the AT1 gene and to examine the role of this polymorphism in acute stroke development. In this study, 257 genomic DNA samples were analysed (from 206 acute stroke patients and 51 healthy individuals). Genomic DNA was prepared from peripheral blood using the salt‐extraction method. The presence of the A1166C polymorphism in the AT1 gene was determined using the polymerase chain reaction (PCR)‐restriction fragment length polymorphism (RFLP) method. PCR products were separated by 2% agarose gel electrophoresis and visualized by a charge‐coupled device (CCD) camera. In this study, the allele frequency at the A1166C position was 92% A and 8% C for control and 97% A and 3% C for patients. This difference in allele frequency between the control group and the patient group was not statistically significant. However, genotype and allele frequencies showed a significant difference (P < 0.001) in the control and the patient groups. The results of this study show no relationship between the A1166C polymorphism in the AT1 gene and acute stroke in the Turkish population.     

Association of AGTR1 (A1166C) and ACE (I/D) Polymorphisms with Breast Cancer Risk in North Indian Population

Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3′ untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women. The polymorphisms were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) respectively. The association between these polymorphisms and BCa risk was estimated by calculating Odds Ratio (OR) and chi-square (χ²) test. The DD genotype/D allele of ACE (I/D) polymorphism and “AC and CC” genotype/C allele of AGTR1 (A1166C) polymorphism were associated with higher risk of BCa when evaluated independently. Furthermore, interaction analysis of “AC and CC” and DD genotype and combination of “C and D” alleles of both polymorphisms revealed significantly greater BCa risk than that observed independently. Conclusively, women harboring “AC or CC” genotype/C allele for AGTR1 (A1166C) polymorphism and DD genotype/D allele for ACE (I/D) polymorphisms have a predisposition to develop more aggressive disease with advanced staging and larger tumor size. Our study indicates importance of genetic screening based on these polymorphisms for women, who may have higher risk of BCa.     

ACE and AGTR1 Polymorphisms in Pathogenesis of Human Left Ventricular Hypertrophy

The A2350G polymorphism of exon 17 of the angiotensin I-converting enzyme gene (ACE) and the A1166C polymorphism of the 3-untranslated region (3-UTR) of the angiotensin II type 1 receptor gene (AGTR1) were tested for association with left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) or arterial hypertension (AH) combined with diabetes mellitus type 2 (DM2). The patients with EH or AH + DM2 did not differ significantly in ACE or AGTR1 allele or genotype frequencies from healthy subjects. Both polymorphisms were associated with LVH in EH. AGTR1 allele 1166C was more frequent in patients with LVH than without (33.6 vs. 20.7%) and affected the left ventricular mass index (LVMI) in patients with EH (p = 0.007). The frequency of ACE allele 2350G in EH patients with LVH was 1.5 times higher, and that of genotype GG was 3.5 times higher, than in patients without LVH. LVMI differed significantly (p = 0.002) between patients with different ACE genotypes, being maximum in homozygotes GG and minimum in homozygotes AA. Thus, AGTR1 allele 1166C and ACE allele 2350G were identified as predisposing to LVH in EH. The two polymorphisms were not associated with the incidence or severity of LVH in patients with AH and DM2.     

Angiotensin II type 1 receptor gene polymorphism and telomere shortening in essential hypertension

Several genetic studies were carried out among hypertensive patients to assess allelic association at the 1166 position of the 3' untranslated region of angiotensin II type 1 receptor gene. In addition, attempts have also been made to find out whether telomere length attrition is associated with hypertension. The main aim of this study was to examine the association of A1166C polymorphism of angiotensin II type 1 receptor and telomere length with essential hypertension in Egyptian people. Angiotensin II type 1 genotyping and relative telomere length were investigated by PCR in 40 patients of essential hypertension and 15 healthy controls. The homozygous AA1166 allele frequency was 92.8% among the studied subjects. There was no intergroup variation in A allele frequency in normotensive group. The frequency of homozygous A allele was significantly higher in hypertensive than normotensive subjects (97.5 and 80%, respectively) with higher frequencies in male patients. The average telomere length ratio was significantly shorter in hypertensive than in normal subjects (1.08?±?0.3 and 1.54?±?0.18, respectively). No correlation was observed between telomere length ratio and body mass index. This study suggests that the homozygous A1166 allele of angiotensin II type 1 and short telomeres may be predisposing factors for essential hypertension in Egyptians and may be involved in the pathogenesis of the disease. Further strategies for treating high-risk patients could result in prevention or delay of end organ damage.     

Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166C (rs106165) genotypes and psoriasis: Correlation with cellular immunity,lipid profile,and oxidative stress markers

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A₁₁₆₆C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A₁₁₆₆C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A₁₁₆₆C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A ₁₁₆₆C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R₁₁₆₆ polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.     

Polymorphism of gene encoding vascular angiotensin II receptor and microangiopathies in patients with insulin-dependent diabetes mellitus

Polymorphism A1166C of the AT1R gene encoding angiotensin vascular receptor [replacement of C (cytosine) for A (adenine)) at position 1166] was compared in patients with insulin-dependent diabetes mellitus (IDDM) complicated by diabetic nephropathy (DN) and in noncomplicated patients (n = 27 and n = 41, respectively) and also in patients with IDDM complicated by diabetic retinopathy (DR) and in correspondent noncomplicated individuals (n = 30 and n = 44, respectively). The frequency of AT1R gene alleles and genotypes in patients with IDDM complicated by DN did not differ significantly from that observed in patients with noncomplicated IDDM. In contrast, in patients with IDDM complicated by retinopathy, a significant decrease in the content of A allele (68.3% against 82.6%) and a significant increase in the content of C allele (31.7% against 17.4%) was found as compared with the control group. Thus, in the Moscow population, A1166C polymorphism of the AT1R gene is not associated with diabetic renal complications but indeed associated with diabetic retinal complications. C allele is a risk factor of DR (the relative risk, RR, is equal to 2.17), and A allele is, in contrast, a protective factor against early retinopathy development (RR is equal to 0.49).     

Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood

In order to investigate the contribution of candidate genes in the renin-angiotensin-aldosterone system (RAAS) in pathogenesis of essential arterial hypertension (EAH), the I/D polymorphism of ACE gene, the M235T polymorphism of the angiotensinogen gene, and the angiotensin II type 1 receptor (AGT,R) A1166C gene polymorphism in a group of children with EAH were analyzed. Fifty-scven children, aged 8-19 years. with the diagnosis of EAH were included in the association study and were compared with 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure measurements higher than 95 age-gender-height percentile of the adopted reference values. A trend was found towards an association between the M235T angiotensinogen gene polymorphism and EAH in childhood in a dominant model (odds ratio (OR) 2.1; 95% confidence interval (CI) 0.9-5.1; P = 0.077), whereas the authors failed to demonstrate an association between the ACE I/D gene polymorphism, or the A1166C AGT1R gene polymorphism and EAH in childhood. Additionally, evidence was found of interaction between the angiotensinogen-TT genotype and obesity on the risk of EAH in childhood (OR 19.3; 95% CI 1.1-77.3; P = 0.014). In conclusion, the M235T angiotensinogen gene polymorphism is considered alone as well as in interaction with obesity to be risk factors for EAH in childhood.     

Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from –0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = –0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis. Received: 23 April 1996 / Revised: 5 August 1996     

Association of Angiotensin II Type 1 Receptor (A1166C) Gene Polymorphism and Its Increased Expression in Essential Hypertension: A Case-Control Study

Objectives

Hypertension is one of the major cardiovascular diseases. It affects nearly 1.56 billion people worldwide. The present study is about a particular genetic polymorphism (A1166C), gene expression and protein expression of the angiotensin II type I receptor (AT1R) (SNP ID: rs5186) and its association with essential hypertension in a Northern Indian population.

Methods

We analyzed the A1166C polymorphism and expression of AT1R gene in 250 patients with essential hypertension and 250 normal healthy controls.

Results

A significant association was found in the AT1R genotypes (AC+CC) with essential hypertension (χ² = 22.48, p = 0.0001). Individuals with CC genotypes were at 2.4 times higher odds (p = 0.0001) to develop essential hypertension than individuals with AC and AA genotypes. The statistically significant intergenotypic variation in the systolic blood pressure was found higher in the patients with CC (169.4±36.3 mmHg) as compared to that of AA (143.5±28.1 mmHg) and AC (153.9±30.5 mmHg) genotypes (p = 0.0001). We found a significant difference in the average delta-CT value (p = 0.0001) wherein an upregulated gene expression (approximately 16 fold) was observed in case of patients as compared to controls. Furthermore, higher expression of AT1R gene was observed in patients with CC genotype than with AC and AA genotypes. A significant difference (p = 0.0001) in the protein expression of angiotensin II Type 1 receptor was also observed in the plasma of patients (1.49±0.27) as compared to controls (0.80±0.24).

Conclusion

Our findings suggest that C allele of A1166C polymorphism in the angiotensin II type 1 receptor gene is associated with essential hypertension and its upregulation could play an important role in essential hypertension.     

Association between the AGTR1 polymorphism +1166A>C and serum levels of high-sensitivity C-reactive protein

Genetic factors have been shown to influence high-sensitivity C-reactive protein (hsCRP) levels, however, which genes that are involved in this process remains to be clarified. The renin–angiotensin system (RAS) is of importance for the regulation of inflammation, and blockade of angiotensin II type 1 receptors (AGTR1) influences hsCRP levels. These findings prompted us to investigate whether a polymorphism in the AGTR1 gene may influence hsCRP levels. Additionally, a polymorphism in the CRP gene that has previously been shown to influence hsCRP levels was genotyped. Serum levels of hsCRP were measured in 270 42-year-old women recruited from the population registry. Two single nucleotide polymorphisms were analysed: +1166A>C and +1444C>T of the AGTR1 and CRP gene, respectively. The A allele of the AGTR1 polymorphism +1166A>C was dose-dependently associated with higher hsCRP levels (p = 0.014, adjusted for confounding factors and multiple comparisons). hsCRP levels were not significantly influenced by the CRP +1444C>T genotype; however, an interaction between the two studied polymorphisms with respect to hsCRP levels was observed (p = 0.018). The significant association between the AGTR1 polymorphism and hsCRP levels, which appears to be independent of anthropometric and metabolic traits, is yet another indication of a direct influence of RAS on inflammation.     

Up-regulation of the cell integrity pathway in saccharomyces cerevisiae suppresses temperature sensitivity of the pgs1Delta mutant

We have previously shown that mutants in the cardiolipin (CL) pathway exhibit temperature-sensitive growth defects that are not associated with mitochondrial dysfunction. The pgs1Delta mutant, lacking the first enzyme of the CL pathway, phosphatidylglycerolphosphate synthase (Pgs1p), has a defective cell wall due to decreased beta-1,3-glucan (Zhong, Q., Gvozdenovic-Jeremic, J., Webster, P., Zhou, J., and Greenberg, M. L. (2005) Mol. Biol. Cell 16, 665-675). Disruption of KRE5, a gene involved in cell wall biogenesis, restores beta-1,3-glucan synthesis and suppresses pgs1Delta temperature sensitivity. To gain insight into the mechanisms underlying the cell wall defect in pgs1Delta, we show in the current report that pgs1Delta cells have reduced glucan synthase activity and diminished levels of Fks1p, the glucan synthase catalytic subunit. In addition, activation of Slt2p, the downstream effector of the protein kinase C (PKC)-activated cell integrity pathway, was defective in pgs1Delta. The kre5W1166X suppressor restored Slt2p activation and dramatically increased (>10-fold) mRNA levels of FKS2, the alternate catalytic subunit of glucan synthase, partially restoring glucan synthase activity. Consistent with these results, up-regulation of PKC-Slt2 signaling and overexpression of FKS1 or FKS2 alleviated sensitivity of pgs1Delta to cell wall-perturbing agents and restored growth at elevated temperature. These findings demonstrate that functional Pgs1p is essential for cell wall biogenesis and activation of the PKC-Slt2 signaling pathway.     

Polymorphisms of angiotensin II type 1 receptor gene and those of angiotensinogen point at culprit artery in ST-segment elevation myocardial infarction

The aim of the study was to determine whether the presence of angiotensin II type 1 receptor 1166A/C gene polymorphism and two polymorphisms of angiotensinogen, namely Met235Thr and Thr174Met, pointed at the culprit artery in patients with ST-segment elevation myocardial infarction (STEMI).