MM Genotype Research Articles

Association between bipolar I disorder and the L55M and Q192R polymorphisms of the paraoxonase 1 (PON1) gene

The purpose of this work was to study the association between the PON1 L55M and Q192R polymorphisms and bipolar I disorder in Tunisian patients and to explore their relation to the sociodemographic, clinical and therapeutic characteristics of this disease. Our study included 109 patients with bipolar I disorder and 110 controls aged 39.4±11.8 and 37.3±9.2 years, respectively. L55M and Q192R of the PON1 gene polymorphisms were determined by multiplex polymerase chain reaction. Significant difference was detected in the distribution of the genotype frequencies of L55M and Q192R polymorphisms (χ²=6.32, df=2, p=0.04; χ²=10.15, df=2, p=0.006 respectively) between patients and controls. We noted significant association between bipolar I disorder and QR and RR genotypes (OR 2.06, CI 95% 1.10-3.84, p=0.02; OR 1.72, CI 95% 1.07-2.75, p=0.02 respectively) and between this disease and LM and MM genotypes (OR 2.22, CI 95% 1.19-4.15, p=0.012; OR 3.04, CI 95% 1.60-5.77, p=0.01 respectively). There were no significant differences in gender, age at onset, illness episode and treatment among all genotypes. However, Q192R polymorphism was significantly associated with age and patients with RR genotype were the youngest. Bipolar I disorder was significantly associated with L55M and Q192R polymorphisms, suggesting that these polymorphisms may play a role for development of bipolar I disorder. There was no significant association between the clinical and therapeutic characteristics of this population and these polymorphisms. Further studies are required to clarify the implication of these polymorphisms in the pathophysiology of bipolar I disorder.

Polymorphisms of pon1 and pon2 genes in hemodialyzed patients

Objectives Q192R, L55M and -108C>T polymorphisms of pon1 gene affect PON1 paraoxonase activity while S311C polymorphism of pon2 gene might be associated with coronary heart disease. The aims of this study were to determine the frequencies of Q192R, L55M, -108C>T and S311C polymorphisms in hemodialyzed patients and to examine the relationship between pon1 gene polymorphisms and PON1 paraoxonase activity in those patients. Design and Methods The study included 238 control subjects and 263 hemodialyzed patients. Results PON1 paraoxonase activity was lower in patients. Genotype frequencies were different between two compared groups only for L55M polymorphism, with control group having higher frequency of MM genotype. Polymorphisms of pon1 gene were associated with significant variation in PON1 paraoxonase activity in both study groups. Conclusion Our results suggest that Q192R, L55M and -108C>T polymorphisms are not by itself the causal factors leading to the lower PON1 paraoxonase activity in hemodialyzed patients.

Polymorphism of the salt sensitivity gene angiotensinogen and gastric cancer risk

A high-salt diet is a risk factor for gastric cancers other than those caused by Helicobacter pylori. The angiotensinogen (AGT) M235T polymorphism has been associated with salt sensitivity. The aim of the present study was to clarify the association between the AGT M235T polymorphism and gastric cancer. The AGT M235T polymorphism was genotyped using PCR-RFLP analysis in 206 gastric cancers and 210control biopsies. A logistic-regression analysis was performed to identify an odds ratio to determine whether a correlation exists between genetic polymorphism and risk in patients with gastric cancer as compared to the control samples. Statistical significance was determined using the Mann Whitney U and Chi-square tests. The genotype distribution was found to be MM=9 (4.4%), MT=57 (27.7%), and TT=140 (67.9%) in samples from patients with gastric cancer and MM=8 (3.8%), MT=60 (28.6%) and TT=142 (67.6%) in the control samples. The odds ratio of gastric cancer of the MM genotype associated with the T carrier was 1.0 (0.4-2.7) (P=0.95). The distribution pattern of AGT M235T polymorphism in the gastric cancer cases and controls was not found to be significantly different in this study. Thus, it can be concluded that other sites of AGT polymorphism or other salt sensitivity genes may be associated with gastric cancer.

Association between paraoxonase-1 gene polymorphisms and risk of metabolic syndrome

Paraoxonase-1 (PON1), a high-density lipoprotein (HDL) associated enzyme, is involved in the metabolism and detoxification of insecticides and pesticides. Three polymorphisms within the PON1 gene affect the enzyme activity. Two of these (L55M and Q192R) are located at the coding region and the third (-107C/T) is in promoter region. We performed a case-control study in order to elucidate the possible contribution of variability within PON1 at three mentioned positions to the risk of MS in a South-East Iranian population. DNA was isolated from peripheral blood of patients (N = 119) with MS and healthy controls (N = 201). Allelic polymorphisms at positions Q192R, L55M and -107C/T in the PON1 gene were studied by Amplification Refractory Mutation System (ARMS)-PCR. It was observed that genotypes RR and QR + RR of Q192R locus significantly increased the risk of MS (OR = 2; 95% CI: 1.17-3.40, P = 0.0001 and OR = 1.62; 95% CI: 1.0-2.63; P = 0.05, respectively). The risk in patients with MM and LM + MM genotypes at the L55M locus was marginal (OR = 1.33; 95% CI: 0.68-1.85; P = 0.34 and OR = 1.12; 95% CI: 0.68-1.85; P = 0.73 respectively). The CC genotype at -107C/T locus also increased the risk of metabolic syndrome, but was not significant. This association was somewhat stronger when combined genotypes at Q192R and L55M loci were analyzed (OR = 3.30; 95% CI: 1.34-8.24; P = 0.007). Our results, in this first study, provide evidence for association of PON1 gene polymorphisms with the risk for metabolic syndrome.

The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients

Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants (p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups (p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.

Evaluating the effects of the c.*1232G > A mutation and TM-QTL in Texel × Welsh Mountain lambs using ultrasound and video image analyses

The c.*1232G > A (MM) mutation in the myostatin gene and TM-QTL are two muscle-enhancing polymorphisms found on Chr 2 and Chr 18, respectively, in Texel sheep. Previous studies on purebred lambs and crossbred lambs out of Mule ewes showed that MM was associated with increased muscle mass and decreased fat content whereas heterozygous TM-QTL lambs had increased loin muscle (M. longissimus lumborum, MLL) depth as measured by ultrasound and increased MLL weight. Welsh Mountain ewes, like Mule ewes, contribute significantly to UK slaughter lamb production from the UK sheep industry's stratified structure. Therefore, this study aimed to evaluate the direct effects of MM and TM-QTL in the genetic background of Texel×Welsh Mountain lambs.Four Texel sires, all MM carriers and two TM-QTL carriers, were used to inseminate Welsh Mountain ewes. Of the 175 lambs born, 130 could be classified for TM-QTL genotype [107 non-carriers (+/+), 23 heterozygous carriers (TM/+)] and 172 for MM genotype [15 non-carriers (+/+), 129 heterozygous carriers (MM/+), 28 homozygous carriers (MM/MM)]. All lambs were weighed at 8 and ∼23weeks of age and were ultrasound scanned before being slaughtered at ∼24weeks of age. All carcasses were graded for conformation and fat class, based on Meat and Livestock Commission (MLC) classification scores, and then scanned using a video image analysis (VIA) system to predict weight of carcass primal cuts and trimmed primal cuts, muscularity traits and carcass shape traits.Carrying two copies of MM was associated with a significant positive effect on 8 weeks weight, a negative effect on ultrasound fat depth and a substantial decrease in MLC-fat score. Two copies of MM also had a strong positive impact on VIA-estimated weight of the hind leg, chump and loin primal cuts, as well as the muscularity of the hind leg and loin regions with greater loin muscle width, depth and area. Homozygous MM carrier lambs had significantly wider carcasses across the shoulders, breast and hind legs and greater areas of the back view of the carcass when measured by VIA. Leg and carcass compactness were also significantly associated with the presence of two copies of MM. However, lambs carrying a single copy of MM were not significantly different to non-carriers in any of the traits measured. TM-QTL significantly increased ultrasound muscle depth and TM-QTL carriers had significantly greater loin muscle width and area measurements. Carcass weight did not differ significantly between genotypic classes for MM or TM-QTL. These results agree in general with other reports of the effects of MM and TM-QTL, in both direction and magnitude, on carcass traits.

Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes

Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; –116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization.

Association of Heme Oxygenase-1 Gene Polymorphisms with Essential Hypertension and Blood Pressure in the Chinese Han Population

Many studies have suggested that heme oxygenase-1 (HMOX1) might be implicated in blood pressure (BP) regulation. We hypothesized that this gene might be responsible for the variation of susceptibility to essential hypertension (EH) and BP and investigated three polymorphisms in HMOX1 (i.e., the (GT)n repeat in the HMOX1 promoter and single-nucleotide polymorphisms (SNPs) rs2071746 and rs2071749) in population-based samples of 789 Han Chinese from Xinjiang, China. The GT repeat numbers ≥33, 27-32, and <27 in the HMOX1 promoter were defined as long (L), middle (M), and short (S) alleles, respectively. The participants carrying SS or SM genotype were sorted into one group, and the participants carrying SL, MM, ML, or LL genotype were sorted into another group. The (GT)n repeat in the HMOX1 promoter showed significant association with EH and BP, whereas SNPs rs2071746 and rs2071749 did not. Compared with the SS+SM (GT)n group, the MM+SL+ML+LL (GT)n group had a lower risk of EH (adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.82; p = 0.002) and lower systolic (128.3 ± 1.3 vs. 132.2 ± 1.0 mm Hg, adjusted p = 0.014) and diastolic BPs (81.7 ± 0.8 vs. 84.5 ± 0.7 mm Hg, adjusted p = 0.009). These findings provide the first genetic evidence for the role of the (GT)n repeat in the HMOX1 promoter in the susceptibility to human EH and the variation of BP.

Genetic aspects of endothelium dysfunction in Uzbek hypertensive patients

The objective of the study was to evaluate the prevalence of ACE/ID, AGT/M235T, AT1R/A1166C, CYP11B2/C344T, B2ВKR/+9-9, ecNOS/4a4b, GNB3/C825T, and ARB2/Gln27Glu gene polymorphisms and their association with endothelium dysfunction (ED) in Uzbek hypertensive patients. The study found an association between ED and AGT M235T gene polymorphism. Genetic models disclosed that the T-allele, MT-, and TT-genotypes of the AGT gene were associated with an increased risk of ED. However, multivariate logistic regression analysis confirmed the negative association between the MM genotype of the AGT gene and positive association between IMT and ED. An association between essential hypertension (EH) in Uzbek males with ACE/ID and GNB3/C825T gene polymorphisms has been demonstrated. There is an association of AGT/M235T gene polymorphism and ED in Uzbek hypertensive patients.

Alpha1‐antitrypsin deficiency–related alleles Z and S and the risk of Wegener's granulomatosis

Deficiency of α(1) -antitrypsin (α(1) AT) may be a determinant of susceptibility to Wegener's granulomatosis (WG). Several previous, mainly small, case-control studies have shown that 5-27% of patients with WG carried the α(1) AT deficiency Z allele. It is not clear whether the S allele, the other major α(1) AT deficiency variant, is associated with WG. This study investigated the relationship of the α(1) AT deficiency Z and S alleles with the risk of developing WG in a large cohort. We studied the distribution of the α(1) AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods. Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2-parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98-2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33-∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele. Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α(1) AT deficiency and susceptibility to WG.

Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico

Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p < 0.05). The heterozygous CT genotype of -108CT polymorphism, the RR genotype of Q192R polymorphism, both LM and MM genotypes of L55M polymorphism, and the haplotypes 221 and 222 (for -108CT, L55M, and Q192R) were associated with the risk for having a child affected by SB (p < 0.02). The heterozygous -108CT genotype was associated only maternally, whereas the heterozygous L55M genotype was relevant only in the fathers. The RR homozygous genotype was relevant both in mothers and fathers, suggesting the importance of this substrate-specific polymorphism. Results suggest that PON1 polymorphisms are relevant risk factors for having offspring affected with SB in this population from Southeast Mexico.

AGT M235T Genotype/Anxiety Interaction and Gender in the HyperGEN Study

BackgroundBoth anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups.MethodologyThe interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style).Principal FindingsAlthough there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype.Conclusion/SignificanceThe results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.

PON1 55 and 192 Gene Polymorphisms in Type 2 Diabetes Mellitus Patients in a Turkish Population

Diabetes mellitus is a multifactorial metabolic disease, caused by the complete or relative absence of insulin hormone, which results in the deterioration of carbohydrate, protein, and lipid metabolism. The PON1 55 and 192 polymorphisms have been reported to be associated with type 2 diabetes and its complications. In this study, the involvement of the PON1 55 and 192 polymorphisms and paraoxonase enzyme activity in diabetic complications was assessed. The MM and QQ genotypes were the most frequent in complications of type 2 diabetes in both of the polymorphisms. PON enzyme activity was lower in the type 2 diabetes group with respect to the control group. Regarding both genotypes and enzyme activity, correlations were found between the PON1 55 and 192 genotypes and diabetic complications. This study thus helps to outline a genotype-phenotype relation for the PON1 gene in a Turkish population.

INTERRELATION OF GENE POLYMORPHISM AND ENDOTHELIUM DYSFUNCTION IN UZBEK HYPERTENSIVE PATIENTS: PP.21.337

Background: Genetic elements contribute to 30–50% of the blood pressure variability. The underlying pathological defect in essential hypertension (EH) is due, at least in part, to endothelial dysfunction (ED). ED is recognized as an early stage in the pathogenesis of EH. Aim of the study was to evaluate the association of gene polymorphisms (ACE/ID, AGT/M235T, AT1R/A1166C, CYP11B2/C344T, BKRB2/ + 9–9, ecNOS/4a4b, GNB3/C825T, ARB2/Gln27Glu) with ED in Uzbek hypertensive men. Methods: The study included 174 nonsmoking men (46.8 ± 9.6 yr) with untreated EH of stage I-II. The total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels were determinated. Low-density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Microalbuminuria was defined as an albumin urinary excretion (AUE) level by immunoturbidimetric assay. Carotid intima-media thickness (IMT) was measured by high-resolution ultrasound. ED was evaluated by measuring of the flowmediated dilatation (FMD) of the brachial artery (BA) with a 7.5 MHz linear array transducer. Genomic DNA was extracted from peripheral blood. PCR-RFLP-based analysis of gene polymorphisms (GP) was performed. Statistical analysis was performed using a Microsoft Office Excel 2007 and Statistica v6.0. Results: Patients were divided into two groups: with δFMD>10% and δFMD < 10% for the determination of GP association with ED. Only the T-allele and MT-, TT-genotypes of the AGT gene were associated with an increased risk for ED: OR 3.18 (95% CI: 1.80–5.63); OR 2.24 (95% CI: 1.08–4.66); OR 15.94 (95% CI: 0.95–268.79). Multivariate logistic regression analysis (dependent variable: δFMD; independent variables: AGT genotype status, age, BMI, SBP, DBP, TC, HDL-C, IMT, AUE, atherogenity index, BA baseline diameter) confirmed the negative association between the MM genotype of the AGT gene, positive association between IMT and ED. We did not find a clear association of ED with other GP. Carriers of C-allele of AT1R gene, -9-allele of B2BKR gene and 4a-allele of ecNOS gene have more disorders of FMD. Conclusions: Only the TT genotype of AGT gene was significantly associated with the risk of ED.

Study on polymerization effect of polyembryony genes by SSCP marker and family trees in Chinese goats

The aim of experiment was to analyze the polymerization effect of genotypes and genotype combinations of PRLR and LHβ gene loci in Xinong Saanen goat by SSCP marker and family trees. The relationships of genotype combinations and litter size were compared in Xinong Saanen goat. The results indicate that there are genetic polymorphisms at the PRLR and LHβ gene loci, and there are 4 positive genotypes (GG, CC, PP and LL) and 4 negative genotypes (HH, DD, QQ and MM) effects on litter size, respectively in Xinong Saanen goat. Compared with the other genotype combinations, the polymerization effect of GGCCPPLL markedly improved (P<0.05). The polymerization effect value of CC genotype was higher than that of CD genotype by 14.12%, and MM genotype was higher than that of LM genotype by 3.80%, and PP genotype was higher than that of QQ genotype by 15.67%, and LL genotype was higher than that of LM genotype by 11.48%, and PQ genotype was higher than that of QQ genotype by 11.02%, and CD genotype was higher than that of DD genotype by 10.69%, and PQ genotype was higher than that of PP genotype by 6.09%. There was significantly polymerization effect in the course of reproduction from parental generation (F0) to F1 generation. However, there was significantly gene isolation effect in the course of reproduction from F1 generation to F2 generation. This result can be used to guide the goat breeding in polyembryony trait.

Angiotensin converting enzyme I/D, angiotensinogen M235T and AT1-R A/C1166 gene polymorphisms in patients with acromegaly

Acromegaly is associated with increased morbidity and mortality related to cardiovascular disease. Hypertension is one of the most common cardiovascular risk factors in acromegalic patients. The aim of this study was to investigate association between the frequencies of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and the angiotensin II type 1 receptor (AT1-R) A/C1166 gene polymorphisms and some clinical parameters of acromegalic patients. Total of 33 acromegalic patients and 63 controls were enrolled to study. We determined the ACE I/D, AGT M235T and AT1-R A/C1166 gene polymorphisms. Serum insulin, glucose, triglyceride, HDL-cholesterol, LDL-cholesterol, growth hormone and Insulin-like growth factor I (IGF-I) levels of subjects were analyzed. The frequencies of ACE and M235T AGT genotype were not significantly different between control and patients. The distribution of AT1R A/C1166 genotypes was significantly different between patients and control subjects (P=0.016). None of the three ACE genotypes, DD, ID and II displayed significant difference in acromegalic patients. A significant difference in systolic blood pressure and the serum IGF-I levels among the three AGT genotype, MM, MT and TT genotypes was found in patient group. Individuals with MT genotypes had significantly higher serum IGF-I levels and systolic blood pressure than MM and TT genotype subjects, P<0.05. In addition, serum triglyceride and HDL levels differed significantly between MM and MT genotypes, P<0.05. However, systolic blood pressure of patients with CC genotypes was found to be significantly higher than AA genotypes individuals in acromegaly group, P<0.05. It can be said that the angiotensinogen MT and AT1R CC1166 genotype carriers may have more risk than other genotypes in the development of hypertension in acromegaly.

ASSOCIATION OF CLINICAL AND GENETIC FACTORS WITH LEFT VENTRICLE HYPERTROPHY IN ARTERIAL HYPERTENSION

Aim. To evaluate association of clinical and genetic factors with left ventricle hypertrophy (LVH) in patients with arterial hypertension (HT). Materials and methods. 672 patients with HT were involved, aged 50,6 y.o. in average, men 67%. Laboratory assays, ECG, echocardiography were performed. Control group included 184 healthy per???sons. Genotyping with single-nucleotide substitutions of the endothelial NO synthase (eNOS) Glu298Asp gene, the C242T of the NADPH oxidase p22phox subunit and the angiotensin 2 receptor type 1 А1166С gene was carried out using a polymerase chain reaction (PCR) with evaluating of restriction fragments length polymorphism, while with substitutions of the angiotensinogen М235Т, G(-6)A gene allele-specific PCR “in real time” was applied. Results. LVH was found in 39% of patients. It was more frequent in persons above 50 years old (OR 2,8, р<0,0001), in men (OR 1,43, p=0,035), in HT of degree 2-3 (OR 3,35, р<0,0001), HT duration more than 5 years (OR 2,52, р<0,05), in obesity (OR 1,57, р=0,005) or diabetes (OR 3,33, р<0,0001) presence. At genetic factors evaluation decrease of LVH risk was revealed in persons with the MM polymorphism of the angiotensinogen М235Т gene (OR 0,506, р=0,0187). Association of the MM genotype with LVH risk lowering was more obvious at the young age (OR 0,31, р=0,018). The A allele of the eNOS gene Glu298Asp polymorphism increased risk of LVH development when HT was diagnosed in the young age (OR 1,98, р=0,037) and in women up to 50 years old (OR 2,34, р=0,027). The T allele of the p22phox NADPH oxidase gene С242Т polymorphism correlated with LVH risk reduction in HT patients up to 50 years old (OR 0,6, p=0,01), the C allele – with increase of it (OR 1,66, р=0,01), this influence was more noticeable in women up to 50 years old (T allele – OR 0,21; C allele – OR 4,57, p=0,001). Conclusion. Hypertensive LVH correlates with age, male gender, HT degree and duration, obesity and diabetes mellitus. Genetic factors were less associated with LVH.

Cathepsin D (C224T) Polymorphism in Sporadic and Genetic Creutzfeldt-Jakob Disease

Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD.

Polymorphism of the prion protein gene PRNP and risk of multiple sclerosis development in ethnic Russians from Bashkortostan

M129V polymorphism of prion protein gene PRNP has been studied in patients with multiple sclerosis (MS) and healthy ethnic Russians from Bashkortostan using allele-specific PCR. The genotype frequency distribution of the examined polymorphism in Russians from Bashkortostan was similar to that in European populations. MM, MV, and VV genotype frequencies in control group and in the MS patients were 50.24%, 42.58%, 7.18% and 43.33%, 45.83%, 10.84%, respectively. It was shown that in the group of MS patients with onset of the disease at the age of 21 and older, the frequency of the VV genotype was higher than in the control group (14.3% versus 6.18%, respectively, P = 0.041). We suggest that the VV genotype is associated with higher risk factor of MS development in the patients aged 21 years and older.

Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome

Introduction Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD). Objectives We evaluated the relationship of tHcy and HTase with paraoxonase 1 ( PON1) gene polymorphism according to CAD severity. Design and methods 118 healthy volunteers and 91 CAD patients were compared. Results Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 48% in CAD patients and were associated with significantly lower levels of HDL cholesterol ( p = 0.02) and 42% of decrease in HTase activities ( p < 0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels ( r = − 0.622, p = 0.00 and r = − 0.355, p = 0.007 respectively) but positively associated with apoB and triglyceride levels ( r = 0.35, p = 0.042 and r = 0.308, p = 0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls ( P < 0.05), while its frequency was similar between the two subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease ( p = 0.029). Conclusions High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients.