Association of permanent arterial hypertension with the renin-angiotensin and kinin-bradykinin system genes in children

A new approach, based on scoring, was proposed for a more objective estimation of the contribution of several genetic variants to a multifactorial disease. Two variants of the approach—genotype scoring and unfavorable factor scoring—were tested by analyzing the polymorphisms of REN (I9–83G>A), AGT (M235T), ACE (I/D), AGTR1 (1166A>C), ATGR2 (3123C>A), and BKR2 (?58T>C and I/D) in children with arterial hypertension (AH). Each of the two variants reported that the genes of the renin-angiotensin and kinin-brady-kinin systems play an important role in permanent AH in girls.     

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.     

F2-Isoprostane level is associated with the angiotensin II type 1 receptor -153A/G gene polymorphism

Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39C[A+1166C] and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.     

Association of polymophisms of renin-angiotensin and hemostasis system genes with ischemic stroke in Russians from central Russia

The allele and genotype frequencies of 14 SNPs of renin-angiotensin (REN, AGT, AGTR1, AGTR2, BKR2, and ADRB2) and hemostasis (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR) system genes, as well as of the ACE insertion-deletion polymorphism, were analyzed in patients with ischemic stroke and in healthy controls matched by age, sex, and ethnicity. Genotyping was performed through the amplification of the selected gene sequences and subsequent hybridization of the labeled fragments with SNP-specific DNA probes on the biochip. There were no significant differences in the allele frequencies of individual genes between the groups of stroke patients and healthy donors. The contribution of the renin-angiotensin and hemostasis system genes to the genetic susceptibility to ischemic stroke in Russians from central Russia was also assessed using the MDR (Multifactor Dimensionality Reduction) approach. The genotype combination FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G, the frequency of which was significantly higher in patients with stroke than in healthy controls, was associated with an increased risk of ischemic stroke (P = 0.03, OR = 2.4, 95%CI 1.1?C5.3).     

Association of genome variations in the renin-angiotensin system with physical performance

Background

The aim of this study was to determine the genotype distribution and allelic frequencies of ACE (I/D), AGTR1 (A +1166 C), BDKRB2 (+9/?9) and LEP (G–2548A) genomic variations in 175 Greek athletes who excelled at a national and/or international level and 169 healthy Greek adults to identify whether some particular combinations of these loci might serve as predictive markers for superior physical condition.

Results

The D/D genotype of the ACE gene (p = 0.034) combined with the simultaneous existence of BDKRB2 (+9/?9) (p = 0.001) or LEP (G/A) (p = 0.021) genotypes was the most prevalent among female athletes compared to female controls. A statistical trend was also observed in BDKRB2 (+9/?9) and LEP (G–2548A) heterozygous genotypes among male and female Greek athletes, and in ACE (I/D) only in male athletes. Finally, both male and female athletes showed the highest rates in the AGTR1 (A/A) genotype.

Conclusions

Our results suggest that the co-existence of ACE (D/D), BDKRB2 (+9/?9) or LEP (G/A) genotypes in female athletes might be correlated with a superior level of physical performance.

     

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.     

Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia

The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.     

Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation

Mutations in the coding region of the angiotensin II type 2 receptor gene (AGTR2) were recently identified to cause X-linked recessive mental retardation. We report a mutation screening of the AGTR2 gene in 57 Finnish male patients with non-syndromic mental retardation. We identified two mutations, a 62GT transversion, which leads to a substitution of glycine for valine (G21V) and a 157AT transversion, which causes a substitution of isoleucine for phenylalanine (I53F). The patients with AGTR2 sequence variants had severe/profound mental retardation, epileptic seizures, restlessness, hyperactivity, and disturbed development of speech.     

A general method for the quantitative analysis of functional chimeras: applications from site-directed mutagenesis and macromolecular association

Two new parameters, I: and C:, are introduced for the quantitative evaluation of functional chimeras: I: (impact) and C: (context dependence) are the free energy difference and sum, respectively, of the effects on a given property measured in forward and retro chimeras. The forward chimera is made by substitution of a part "a" from ensemble A into the analogous position of homologous ensemble B (S:(B --> A)). The C: value is a measure of the interaction of the interrogated position with its surroundings, whereas I: is an expression of the quantitative importance of the probed position. Both I: and C: vary with the evaluated property, for example, kinetics, binding, thermostability, and so forth. The retro chimera is the reverse substitution of the analogous part "b" from B into A, S:(A --> B). The I: and C: values derived from original data for forward and retro mutations in aspartate and tyrosine aminotransferase, from literature data for quasi domain exchange in oncomodulin and for the interaction of Tat with bovine and human TAR are evaluated. The most salient derived conclusions are, first, that Thr 109 (AATase) or Ser 109 (TATase) is an important discriminator for dicarboxylic acid selectivity by these two enzymes (I: < -2.9 kcal/mol). The T109S mutation in AATase produces a nearly equal and opposite effect to S109T in TATase (C: < 0.4 kcal/mol). Second, an I: value of 5.5 kcal/mol describes the effects of mirror mutations D94S (site 1) and S55D (site 2) in the Ca(2+) binding sites of oncomodulin on Ca(2+) affinity. The second mirror set, G98D (site 1) and D59G (site 2), yields a smaller impact (I: = -3.4 kcal/mol) on Ca(2+) binding; however, the effect is significantly more nearly context independent (C: = -0.6 versus C: = -2.7 kcal/mol). Third, the stem and loop regions of HIV and BIV TAR are predominantly responsible for the species specific interaction with BIV Tat(65-81) (I: = -1.5 to -1.6 kcal/mol), whereas I: = 0.1 kcal/mol for bulge TAR chimeras. The C: values are from -0.3 to -1.2 kcal/mol. The analysis described should have important applications to protein design.     

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

Background

Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population.

Methods

The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications.

Results

Seven polymorphisms were found being associated with risk of asthma, namely: A Disintegrin and Metalloprotease 33 (ADAM33) T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73), Angiotensin-Converting Enzyme (ACE) D/I (OR = 3.85, 95%CI: 2.49-5.94), High-affinity IgE receptor β chain (FcεRIβ) -6843G/A (OR = 1.49, 95%CI: 1.01-2.22), Interleukin 13(IL-13) -1923C/T (OR = 2.99, 95%CI: 2.12-4.24), IL-13 -2044A/G (OR = 1.49, 95%CI: 1.07-2.08), Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) -28C/G (OR = 1.64, 95%CI: 1.09-2.46), Tumor Necrosis Factor-α (TNF-α) -308G/A(OR = 1.42, 95%CI: 1.09, 1.85). After subgroup analysis by age, the ACE D/I, β2-Adrenergic Receptor (β2-AR) -79G/C, TNF-α -308G/A, Interleukin 4 receptor(IL-4R) -1902G/A and IL-13 -1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the ACE D/I, FcεRIβ -6843G/A, TNF-α -308G/A, IL-13 -1923C/T and IL-13 -2044A/G polymorphisms were associated with asthma risk in Chinese adults.

Conclusion

ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.     

Asthma susceptible genes in Chinese population: A meta-analysis

Background

Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population.

Methods

The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications.

Results

Seven polymorphisms were found being associated with risk of asthma, namely: A Disintegrin and Metalloprotease 33 (ADAM33) T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73), Angiotensin-Converting Enzyme (ACE) D/I (OR = 3.85, 95%CI: 2.49-5.94), High-affinity IgE receptor β chain (FcεRIβ) -6843G/A (OR = 1.49, 95%CI: 1.01-2.22), Interleukin 13(IL-13) -1923C/T (OR = 2.99, 95%CI: 2.12-4.24), IL-13 -2044A/G (OR = 1.49, 95%CI: 1.07-2.08), Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) -28C/G (OR = 1.64, 95%CI: 1.09-2.46), Tumor Necrosis Factor-α (TNF-α) -308G/A(OR = 1.42, 95%CI: 1.09, 1.85). After subgroup analysis by age, the ACE D/I, β2-Adrenergic Receptor (β2-AR) -79G/C, TNF-α -308G/A, Interleukin 4 receptor(IL-4R) -1902G/A and IL-13 -1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the ACE D/I, FcεRIβ -6843G/A, TNF-α -308G/A, IL-13 -1923C/T and IL-13 -2044A/G polymorphisms were associated with asthma risk in Chinese adults.

Conclusion

ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.     

Transgene number-dependent, gene expression rate-independent rejection of Dd -, Kd-, or Dd Kd -transgened mouse skin or tumor cells from C57BL/6 Db Kb mice

Recipient cells migrating into the transplantation site of an allograft recognize histocompatibility antigens on the grafts and are cytotoxic against the grafts. Although the alloreactive immune response is predominantly directed at the major histocompatibility complex (major histocompatibility complex [MHC]; H-2 in mice) class I molecules, the basic mechanisms of allograft rejection (e.g., ligand-receptor interaction) remain unclear, because of the polymorphism and complexity of the MHC. To examine the role of MHC class I molecules in allograft rejection, D(d) , K(d) or D(d) K(d) -transgenic skin or tumor cells we established on a C57BL/6 (D(b) K(b) ) background and transplanted into C57BL/6 mice. Skin grafts from allogeneic (i.e., BALB/c, B10.D2, and BDF1) strains of mice were rejected from C57BL/6 mice on days 12-14 after grafting, whereas isografts were tolerated by these mice. Unexpectedly, skin grafts from D(d) -, K(d) -, and D(d) K(d) -transgenic C57BL/6 mice were rejected on days 12-14 in a transgene expression rate-independent manner from 9/19 (47%), 20/39 (51%), and 12/17 (71%) of C57BL/6 mice, respectively. Similarly, intradermally transplanted allogeneic (i.e., Meth A), but not syngeneic (i.e., EL-4), tumor cells were rejected from C57BL/6 mice; the growth of D(d) - or K(d) -transfected EL-4 cells was delayed by 10-13 days; and 4/10 (40%) of D(d) K(d) -transfected tumor cells were rejected from C57BL/6 mice. These results indicate that D(d) and K(d) genes are equivalent as allogeneic MHC class I genes and that C57BL/6 (D(b) K(b) ) mice reject D(d) -, K(d) -, or D(d) K(d) -transgened skin or tumor cells in a transgene number-dependent, gene expression rate-independent manner.     

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.     

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.     

活细胞内MGTR1-3＇UTR的荧光标记及应激定位分析

利用噬菌体衣壳蛋白MS2和带有序列特异性茎环结构（含有MS2蛋白结合位点）的RNA之间的高度亲和力,对外源性入血管紧张素l型受体（angiotensin II receptor type1,AGTRl）mRNA3’端非翻译区（3＇untranslated region,3’UTR）片段进行红色荧光标记,进而在活细胞（HeLa）内研究该mRNA片段的应激生物学行为。通过在pSG5空载体质粒上先后插入两个双链DNA目的片段AGTR1-3qATR和24×MS2,构建重组质粒pSG5／AGTR1—3‘UTR／24×MS2,并将该质粒与重组质粒pERFP／MS2和pEGFP／C1-G3BP共转染入Hela细胞。荧光显微成像结果显示,AGTR1-3UTR-24×MS2 mNA片段能够携带具有入核信号的MS2-RFP融合蛋白离开胞核进入胞浆,而且在亚砷酸盐刺激下,红色荧光标记的AGTR1-3＇UTR-24×MS2 mRNA;4段可在胞浆中形成与应激蛋白G3BP—GFP共定位的颗粒。该结果表明,针对AGTR1-3‘UTR片段的MS2-RFP荧光标记系统构建成功,该荧光标记系统能有效避免假阳性的荧光信号。在细胞受到氧化应激时,AGTR1-3’UTR会被招募至胞浆中的应激颗粒结构中,启示了AGTR1-3＇UTR区域对于调控AGTR1 mRNA在细胞内的应激定位具有重要作用。     

Identification and determination of material properties for porohyperelastic analysis of large arteries.

A "porohyperelastic" (PHE) material model is described and the theoretical framework presented that allows identification of the necessary material properties functions for soft arterial tissues. A generalized Fung form is proposed for the PHE constitutive law in which the two fundamental Lagrangian material properties are the effective strain energy density function, W(e), and the hydraulic permeability, kij. The PHE model is based on isotropic forms using W(e) = Ue (phi) = 1/2C0(e phi - 1) and the radial component of permeability, kRR = kRR(phi), with phi = C1'(I1 - 3) + C2'(I2 - 3) + K'(J - 1)2. The methods for determination of these material properties are illustrated using experimental data from in situ rabbit aortas. Three experiments are described to determine parameters in Ue and kRR for the intima and media of the aortas, i.e., (1) undrained tests to determine C0, C1', and C2'; (2) drained tests to determine K'; and (3) steady-state pressurization tests of intact and de-endothelialized vessels to determine intimal and medial permeability (adventitia removed in these models). Data-reduction procedures are presented that allow determination of kRR for the intima and media and Ue for the media using experimental data. The effectiveness and accuracy of these procedures are studied using input "data" from finite element models generated with the ABAQUS program. The isotropic theory and data-reduction methods give good approximations for the PHE properties of in situ aortas. These methods can be extended to include arterial tissue remodeling and anisotropic behavior when appropriate experimental data are available.     

Polymorphism of genes of the renin-angiotensin system ACE, AT1R, and AT2R in patients with pulmonary tuberculosis

The goal of this work was to verify the hypothesis about the possible role of some genes of the renin-angiotensin system in the innate immunity to tuberculosis. The insertion/deletion polymorphism (I/D) of the gene of the angiotensin-converting enzyme (ACE) is known to have an effect on the concentration of the angiotensin II in human body and also an indirect effect on various branches of metabolism. On the one hand, people with homozygote deletion of the ACE gene (DD genotype) are vulnerable to adiposity, arterial hypertension, hypercholesterolemia, and a number of other pathological conditions. On the other hand, it was shown that hypocholesterolemia is the general phenomenon for the patients with pulmonary tuberculosis (Perez-Guzman C. et al., Chest (2005)). In this work, we studied the I/D polymorphism of the gene ACE (genotypes DD, ID, and II), single nucleotide polymorphism (SNP) of the gene AT1R (1166 A/C), and SNP in 3123 positions of the gene AT2R (3123 A/C) in 200 patients with tuberculosis, 202 patients with essential hypertension, and 208 apparently healthy subjects. A group of patients with essential hypertension was used as a contrast group. According to the hypothesis stated above, the excess in the number of patients with the DD genotype (ACE) should be statistically significant in the group of patients with hypertension as compared to the group of patients with tuberculosis (chi2 = 9.64; chi2 = 0.0019; OR = 2.0; CI 1.2-3.3). There was a trend toward an increase in the rate of the DD genotype in the group of patients with tuberculosis relative to healthy subjects. Similar trend was observed in healthy subjects relative to the group of patients with hypertension. However, this difference was found to be statistically insignificant. The genotypes and allelotypes were compared in the group of patients with tuberculosis versus both the two control groups (healthy subjects and patients with hypertension). The significant difference from control was observed only in male rather than female patients with tuberculosis. It was shown that the greatest contribution to the distinction between groups was due to the genes ACE and AT2R. The combination of the genotypes of genes ACE and AT2R (ID+3123C) was met significantly more frequently in male patients with tuberculosis as compared to control group of healthy subjects (chi2 = 9.70; chi2 = 0.002; OR = 2.3; CI 1.2-4.3). The results obtained in this work are discussed in terms of the hypothesis stated above.     

Association of polymorphic markers of chemokine genes,their receptors,and <Emphasis Type="Italic">CD14</Emphasis> gene with coronary atherosclerosis

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo and Markov chain (APSampler) method, allele/genotype combinations associated with both low and high CA risk were revealed. The most important findings included the following: CXCR4*T/T + CCL2*C + CCR5*I/I (P_perm = 1 × 10^–6, OR = 0.44, 95% CI 0.3–0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P_perm = 4 × 10^–6, OR = 5.78, 95% CI 2.34–14.28), CD14*C + CCL2*C/C + CCR5*D (P_perm = 6.3 × 10^–6, OR = 5.81, 95% CI 2.17–15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P_perm = 0.01, OR = 3.21, 95% CI 1.63–6.31).