Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system. The apolipoprotein E (APOE) and interleukin 1 β (IL1B) genes are considered to be candidate genes of MS. The aim of the study was to examine the hypothesis of the importance of APOE and IL1B gene polymorphisms in MS development in ethnic Tatars. DNA samples isolated by phenol-chloroform extraction from peripheral blood of 383 ethnic Tatars (120 MS patients and 263 healthy donors) were studied. 112C/R and 158R/C APOE gene polymorphisms as well as ?511T/C IL1B gene polymorphism were analyzed by polymerase chain reaction (PCR) followed by PCR product digestion by endonuclease. Odds ratio (OR) values were used for evaluation of the relative risk of alleles and(or) genotype combinations. It has been shown that APOE*2/*3 genotype is associated with low risk of the disease development (OR = 0.20) in women. A combined effect of APOE and IL1B allelic variants has been discovered indicating the increased risk of the disease development in the carriers of APOE*4 and IL1B*T/*T alleles (OR = 4.76).     

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol–chloroform extraction by the standard method. IL6 −572 G/C, IL12B 1159 C/A, and IL10 –627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 −627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 −572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 −627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 −627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.     

Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan

The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and Russians) living in Republic Bashkortostan. Statistically significant differences in the distribution of DBP gene genotypes between Tatars and Russians (chi2 = 8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution within DBP gene was similar in healthy control subjects of both ethnic groups, with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development: the frequency of GC*1F/1S genotype in COPD patients was significantly lower than in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor = 0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the same group had higher frequency of GC* 1F/2 genotype than healthy individuals (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95% 1.067-6.20). In Russian population the distribution of alleles and genotypes of DBP gene were similar in COPD patients and healthy individuals.     

Paraoxonase 1 gene polymorphism 192Q/R in old men and long-livers from Tatars ethnic group

Comparison in genotype and allele frequencies of people groups of younger (from 1 till 20 years), middle (21-55 years), elderly (56-74 years), senile (75-89 years) age and long-livers (90-109 years) have been performed (only 1116 person) with the purpose of analysis of molecular-genetic bases of ageing and longevity of the person. Allele variants of PON1 gene have been identified by polymerase chain reaction in a combination with restriction analysis. In the general sample of Tatars genotypes PON1*Q/*Q, PON1*Q/*R and PON1*R/*R are revealed with frequencies of 46.15, 44.35 and 9.5%, alleles PON1*Q and PON1*R are found with frequencies of 68.32 and 31.68% accordingly. Statistically significant distinctions on frequencies of genotypes and alleles between separate age groups are found. It has appeared, that frequency of PON1*R allele (28.46%) is lowered among old men in comparison with those among persons of younger age (37.42%, P = 0.009). However essentially above in group of long-livers, than in group of old men, frequencies allele PON1*R (P = 0.005) and genotype PON1*R/*R (P = 0.01).     

Association of YWHAE gene polymorphism with suicidal behavior

The importance of YWHAE gene polymorphisms (rs1532976, rs3752826, and rs9393) in the development of suicidal behavior has been studied in ethnic groups of Russians and Tatars from the Republic of Bashkortostan. It was revealed that the carriers of the YWHAE*C allele of rs3752826 polymorphism of the YWHAE gene have increased the risk of suicidal behavior (OR = 1.91), regardless of their ethnicity. In addition, the YWHAE*T allele of rs9393 polymorphism (OR = 2.21), YWHAE*T/*T genotype (OR = 2.73), and YWHAE*T allele (OR = 1.52) of the rs1532976 polymorphism, as well as the YWHAE*A*T haplotype of rs1532976 and rs9393 polymorphisms (OR = 1.54) represent genetic markers of the risk of suicidal behavior in the sample of subjects of Russian ethnicity.     

Polymorphism of the apolipoprotein E gene and risk of multiple sclerosis in ethnic Russians

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system with pronounced hereditary predisposition. The purpose of the study was to test the assumption on the involvement of the apolipoprotein E gene (APOE) polymorphism in exon 4 in the development of MS in ethnic Russians. Samples independently collected in Moscow (106 MS cases and 189 control healthy volunteers), Sverdlovsk oblast (54 and 109, respectively), and the Republic of Bashkortostan (119 and 285, respectively) were examined. Genotypes for 2059C/T and 2197C/T polymorphisms of the APOE gene, which determine the amino acid substitutions C112R and R158C in apolipoprotein E, were analyzed by polymerase chain reaction followed by restriction analysis of amplificates. No statistically significant differences in genotype or allele frequencies were found between the control group and the group of MS cases. The APOE*4 allele is not associated with the risk of MS in ethnic Russians.     

Variations in APOE genotype distribution in children from areas with different adult cardiovascular disease mortality in Spain

We investigate whether a varying distribution of the APOE genotype could help explain regional differences in ischemic heart disease (IHD) mortality in Spain. APOE genotypes were examined by PCR in 1,274 randomly selected healthy children from four Spanish regions with different adult IHD mortality rates (northwest and central Spain with low rates and southeast and southern Spain with high rates). In the population as a whole the prevalence of the higher risk APOE*3/*4 genotype is 16.8% and the prevalence of the APOE*4 allele is 10.1%. In northwest Spain the frequencies of the APOE*3/*4 genotype (12.9%) and of the APOE*4 allele (8.3%) are smaller than in the other regions. The southeast region shows statistically higher frequencies of the APOE*3/*4 genotype (22.5%) and of the APOE*4 allele (13.2%) than in the other regions or in the group as a whole. We can conclude that Spain is not homogeneous in terms of APOE genotype distribution. Although the prevalence of the APOE*4 allele is generally low, there are areas with higher prevalence of the APOE*4 allele and a higher incidence of adult IHD mortality. This allows us to conclude that in Spain this genetic determinant can be associated with IHD mortality in relatively isolated populations.     

Polymorphic variants of genes encoding interleukin-6 and fibrinogen, the risk of ischemic stroke and fibrinogen levels

Carriage frequencies of alleles and genotypes of polymorphous locus of -174G>C IL6 (rs1800795) were analyzed in the patients with ischemic stroke (IS) of Russian ethnic descent (200 cases) and in the control group of the same ethnic descent with similar sex and age (140 controls). Significant differences were identified in frequencies of carriage (in homo- or heterozygous form) of allele IL6*-174G (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered as risk factor for IS and in frequencies of IL6*-174C/C genotype carriage, correspondingly (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69). After sex stratification of patients and controls similar significant differences were observed only between female patients and controls, after age stratification the difference was observed only for the age group older 60 years. Complex analysis of association of SNP -174G>C IL6 alleles and genotypes carriage in combination with SNP 4266A>G (Thr312Ala) FGA (rs6050) (see symbol) -249C>T FGB (rs1800788) with IS revealed protective combinations IL6*-174C/C + FGA* 4266A (see symbol) IL6*-174C/C + FGB*-249C, which were slightly more significant than single protective genotype IL6*-174C/C associated with IS and their ORs didn't differ substantially from the single genotypes's OR value. At the same time the combinations of alternative allele IL6*-174G with the same FGB*-249C or FGA* 4266A alleles were revealed and their association significance levels as well as OR values were lower than the values for the single risk allele IL6*-174G. In case of the mutual carriage of IL6*-174G allele with FGA*4266A/A, FGB*-249C/C genotypes or with combinations of these alleles/genotypes the "neutralized" effect became stronger. In other words, we observed association of IS with allele/genotype combinations of genes IL6, FGA and FGB, in which IL6 plays key role and FGA and FGB have modulating function. In analysis of association of fibrinogen plasma levels with three analyzed polymorphous loci significant differences were not revealed.     

Associations of Polymorphic DNA Markers and Their Combinations with Multiple Sclerosis

Multiple sclerosis (MS) is regarded as multifactorial, polygenic disease; its development is the result of autoimmune and neurodegenerative processes which lead to multifocal lesions of the central nervous system. The aim of the study was to analyze associations between MS and polymorphic markers rs3129934 (C6orf10), rs1109670 (DDEF2/MBOAT2 gene), rs9523762 (GPC5 gene), rs28362491 (NFKB1 gene), rs10974944 (JAK2 gene), and rs2304256 (TYK2 gene). The material for the study was DNA samples of unrelated MS patients (N = 224) aged 17 to 67 years and individuals of a control group (N = 312) aged 18 to 66 years. Both samples were formed from the ethnic group of Russians. The results of the investigation demonstrated that, for women, MS was associated with genotypes rs3129934*C/T (p = 0.001, OR = 2.23), rs3129934*T/T (p = 0.028, OR = 4.04), and rs2304256*C/C (p = 0.049, OR = 1.6); for men, with genotype rs1109670*C/A (p = 0.017, OR = 2.06). In addition, using the APSampler algorithm, we identified combinations of alleles associated with increased risk of MS separately for women and men, in which the most frequent alleles of polymorphic markers were rs3129934*T, rs1109670*C, rs10974944*G, and rs2304256*C.     

CYP1A1 *2B and *4 polymorphisms are associated with lung cancer susceptibility in Mexican patients

BACKGROUND: CYP1A1 is a gene involved in the high aryl hydrocarbon hydroxylase -inducible phenotype, which is a genetically-determined variation among individuals that has been associated with lung cancer risk. More specifically, CYP1A1 *2B and *4 polymorphisms have been associated with high susceptibility to lung cancer among cigarette smokers. MATERIALS AND METHODS: DNA was obtained from blood samples and we studied by PCR-RFLP the distribution of CYP1A1 *2B (n=248) and *4 (n=222) polymorphisms in healthy controls and 222 lung cancer patients from a Mexican population. RESULTS: Comparisons between groups showed an increased risk for lung cancer patients of *2B/*2B (18%; OR 7.6; 95% CI 3.0-19.2) and *4/ *4 genotypes (15%; OR 11.45; 95% CI 2.19-59.85) compared to the control group (1% for *2B/ *2B and 4.4% for *4/ *4). A significant association between lung cancer and homozygous *2B/ *2B passive smokers and *4/*4 ever (cigarettes) and passive smokers was also observed (p<0.05). Multivariate analysis revealed an increased risk for the *2B/*2B genotype (OR 6.83), as well as for *4/*4 (OR 28.8). CONCLUSION: The results of the study indicate a significant association between *2B/*2B and *4/*4 genotypes and the risk of developing lung cancer among Mexicans.     

The frequency and distribution of thiopurine S-methyltransferase alleles in south Iranian population

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Variability in TPMT activity is mainly due to genetic polymorphism. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in an Iranian population from south of Iran (n = 500), using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. Four hundred seventy four persons (94.8%) were homozygous for the wild type allele (TPMT*1/*1) and twenty five people were TPMT*1/*3C (5%). One patient was found to be heterozygous in terms TPMT*1 and *2 alleles with genotype of TPMT*1/*2 (0.2%). None of the participants had both defective alleles. The TPMT*3C and *2 were the only variant alleles observed in this population. The total frequency of variant alleles was 2.6% and the wild type allele frequency was 97.4%. The TPMT*3B and *3A alleles were not detected. Distributions of TPMT genotype and allele frequency in Iranian populations are different from the genetic profile found among Caucasian or Asian populations. Our findings also revealed inter-ethnic differences in TPMT frequencies between different parts of Iran. This view may help clinicians to choose an appropriate strategy for thiopurine drugs and reduce adverse drug reactions such as bone marrow suppression.     

Cytokine gene polymorphisms in endemic pemphigus foliaceus: a possible role for IL6 variants

Endemic pemphigus foliaceus (EPF) is a complex autoimmune disease characterized by the presence of antibodies against desmoglein 1, which lead to the loss of adhesion among keratinocytes (acantholysis). Variants of HLA class II genes have been the only genetic factors found to modulate susceptibility to EPF. This study aims at investigating the influence of cytokine genetic variants in the pathogenesis of EPF, since they may affect the expression levels of these immunomodulatory molecules. The sample included 168 patients and 189 controls and was comprised of mostly Caucasoids and Mulattos. The approach consisted of a case-control association study and the alleles were identified by mismatched PCR-RFLP. No associations were found with variants of IL1A, IL1B, IL1RN, IL4R and IL10. There was a weak negative association with the haplotype -1082G -592C (OR=0.49) of the IL10 gene in Mulattos. In regard to polymorphism -590 of the IL4 gene, a positive association with the T/T genotype (OR=2.71) and a negative association with the C variant (OR=0.37) were found. Associations with IL6 -174 variants suggest that the C/C genotype has a protective effect (OR=0.13) while carriers of the G allele are more susceptible (OR=7.66) to EPF.     

Association of cytochrome P450 genes polymorphisms (CYP1A1 and CYP1A2) with the development of chronic obstructive pulmonary disease in Bashkortostan

To assess the role that polymorphisms of cytochrome P450 genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of CYPIA1 (2455 A/G, 3801T/C) and CYP1A2 (-2464T/delT, -163C/A) genes were studied in Tatar and Russian COPD patients and in cases of healthy individuals (Russian, Tatar and Bashkir), residents of Bashkortostan. It was shown that the CYP1A1 and CYP1A2 genes haplotypes frequency distribution patterns do not differed between Tatars and Russians ethnic groups (chi2 = 0.973, df = 3, p = 1.00 and chi2 = 1.546, df = 3, p = 0.92, respectively). Analysis of the the CYP1A1 and CYP1A2 genes haplotypes revealed statistically significant differences in the haplotypes frequency distributions between Bashkirs versus Russians and Tatars (chi2 = 12.328, df= 3,p = 0.008; chi2 = 9.218, df=3, p = 0.034, respectively for CYP1A1 gene and (chi2 = 18.779, df=3, p = 0.0001, chi = 14.326, df=3, p = 0.003, respectively for CYP1A2 gene). The (-2467)delT allele and CYP1A2*1D haplotype of CYPIA2 gene was associated with higher risk of COPD in Tatar ethnic group (OR = 1.83, 95% CI 1.24-2.71, chi2 = 9.48, p = 0.003 and chi2 = 9.733, p = 0.0027, Pcor = 0.008; OR = 3.908, 95% CI 1.56-10.19, respectively). On the other hand the CYP1A2*1A haplotype had protective effect (chi2 = 6.319, p = 0.0127, Pcor = 0.038; OR = 0.6012, 95% CI 0.402-0.898). But at the same time we did not find any differences in the genotypes and haplotypes frequency distributions of the CYP1A2 gene within the patients and healthy groups in Russian ethnic group. We also did not find any association of CYP1A1 gene with COPD in ethnic groups of Bashkortostan.     

Role of CYP2C9 and CYP2C19 polymorphisms in patients with atherosclerosis

The arachidonic acid metabolizing CYP enzymes with prominent roles in vascular regulation are epoxygenases of the two gene family which generate epoxyeicosatrienoic acids. Carriers of CYP2C9 mutant alleles exhibit a diminished CYP2C9 metabolic capacity leading to decreased endothelium-derived hyperpolarizing factors (EDHF) synthesis and an increased risk for atherosclerosis. We investigated whether the polymorphisms of CYP2C9/19 are related with atherosclerosis. We examined 108 patients having angioraphically > or =70 coronary artery narrowing and 90 healthy controls. CYPC2C9/19*2 and CYP2C9/19*3 alleles were investigated in both patients and controls by a real time PCR instrument. There was no significant difference in the distribution of the CYP2C9*2/*3 alleles between cases and the controls. We found that smoker patients having CYP2C9*2 heterozygote genotype have 3.7-fold risk of developing atherosclerosis. CYP2C19*3 heterozygote alleles are more frequent in patients than in controls (10.2%, 5.6% respectively) and it is related with a three-fold risk of atherosclerosis (odds ratio (OR) = 3.75, confidence interval (CI) = 0.75-18.65). It becomes clear that cigarette smoking can cause almost all major diseases prevalent today, such as cancer or heart disease. This inter-subject variability in cigarette-induced pathologies is partly mediated by genetic variants of genes that may participate in detoxification processes, e.g., cytochrome P450 (CYP), cellular susceptibility to toxins, such as p53, or disease development such as atherosclerosis.     

Genetic variants of the paraoxonases (PON1 and PON2) in the Chilean population

We estimated the frequencies of PON1 and PON2 variants (linked genes) in two hospital samples taken from the northern (San José Hospital, SJH) and eastern (Clínica Las Condes, CLC) parts of Santiago, Chile, using the polymerase chain reaction followed by restriction endonuclease digestion. The two hospital samples have different degrees of Amerindian admixture (SJH, 34.5%; CLC, 15.9%), which is reflected in the observed frequencies of the PON1 *B allele (SJH, 43.1%; CLC, 33.7%) and the PON2*S allele (SJH, 86.3%; CLC, 77.6%); both allele frequencies are significantly different between samples. The frequencies of the combined PON1-PON2 genotypes *A/*B-*C/*C, *A/*B-*S/*S, and *B/*B-*S/*S and of the haplotypes PON*A,C and PON*B,S were significantly different between the SJH and CLC groups. None of the genotype frequencies deviated significantly from those predicted by the Hardy-Weinberg equation. No linkage disequilibrium was found between the PON1 alleles and any of the PON2 alleles in either group (all p > 0.05). In our samples 38.52% (SJH) and 26.25% (CLC) of chromosomes must have the haplotype PON*B,S, presumed to be related to the risk of coronary artery disease. Twenty-four of 193 (12.4%) SJH individuals and 7 of 122 (5.7%) CLC individuals were homozygotes for this haplotype. Finally, our data indicate ethnic-group-dependent genetic differences in the vulnerability to toxic organophosphorus.     

Effect of apolipoprotein E genotype and saturated fat intake on plasma lipids and myocardial infarction in the Central Valley of Costa Rica

We assessed the effect of APOE polymorphisms -491 A/T, C112R (APOE*4), and R158C (APOE*2) and saturated fat intake on plasma lipid levels and risk of myocardial infarction (MI) in 1,927 case subjects and 1,927 population-based control subjects matched for age, sex, and residence, all living in the Central Valley of Costa Rica. A significant gene-diet interaction (p = 0.0157) was observed. High saturated fat intake was associated with a 49% increased risk of MI (OR = 1.49; 95% CI, 1.16-1.92) among wildtype subjects. In contrast, high saturated fat intake was associated with a 2.2-fold increased risk of MI among carriers of APOE*2 (OR = 3.17; 95% CI, 1.58-6.36) and with a 1.6-fold increase among carriers of the -491T and APOE*4 variants together (OR = 2.59; 95% CI, 1.38-4.87). Consistently, a high fat diet elicited a greater response in LDL cholesterol among carriers of APOE*2 (+ 17%) and APOE*4 (+ 14%) compared to noncarriers (+6%). The frequency of APOE variants was similar in case and control subjects, although APOE*4 homozygotes were at increased risk of MI compared to noncarriers (OR = 2.26; 95% CI, 1.03-4.98). This study supports the hypothesis that the APOE*2 and APOE*4 variants increase susceptibility to MI in the presence of high saturated fat and could explain inconsistent findings on the effects of these variants on MI in various populations.     

Polymorphism of the APOE locus in the Azores Islands (Portugal)

Our aim in this study is to report on the polymorphism of the APOE gene in the Azores Islands (Portugal) to obtain a population baseline of the existing variation in this locus, known to be one of the genetic determinants of plasma lipid levels. One hundred twenty-six Azorean individuals were typed for the APOE polymorphism using standard PCR-RFLP. Allele frequencies obtained for APOE*2, APOE*3, and APOE*4 were 6.75%, 83.73%, and 9.52%, respectively. The APOE*3/*3 genotype presented the highest frequency (69.84%), and the APOE*4/*4 genotype had the lowest frequency (0.79%). Genotype frequencies were in conformity with Hardy-Weinberg expectations. The observed genotype and allele frequencies were similar to those reported for other Iberian samples. Furthermore, Nei's gene diversity (H = 0.2864 +/- 0.0351) was similar to that reported for samples from mainland Portugal. The data generated from this study will be of importance in the context of ongoing studies concerning the factors that influence lipid levels in the Azorean population.     

Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.     

Association between the APOE*4 allele and atherosclerosis is age dependent among Argentine males

Several studies have shown evidence of an association between the *4 allele of apolipoprotein E (APOE) and coronary heart disease (CHD) in different populations. We determined the APOE genotype and total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC) values in 189 patients with angiographically evaluated atherosclerosis. The APOE*4 allele was found to be statistically significantly more frequent (odds ratio, 1.93; 95% confidence interval, 1.12-3.32) among male patients than in a randomly chosen population-based sample. No significant difference was found when female patients were compared to the general population. The APOE*4 allele was found primarily among young (30-45-year-old) male patients (p < 0.04). Despite the ascending linear tendency of the mean TC values for genotypes APOE*2/*3, APOE*3/*3, and APOE*3/ *4 reported in our case population, no differences were observed among our patients. We conclude that the APOE*4 allele is associated with an increased risk for atherosclerotic vascular disease, that this association has an age-dependent effect, and that it acts as a genetic factor that increases susceptibility to developing the disease in young to middle-aged male adults in our population.     

ACE I/D polymorphism in Alzheimer’s disease

Angiotensin-converting enzyme (ACE) has been reported to show altered activity in patients with neurological diseases. The recent studies found that a 287 bp insertion/deletion (I/D) polymorphism of the ACE gene may be associated with susceptibility to Alzheimer’s disease (AD) but the results have been heterogenous between studies in Europe. In the present study we examined for the first time the association of ACE I/D polymorphism along with APOE genotype in 70 sporadic AD and 126 control subjects in Slovak Caucasians (Central Europe). An increased risk for AD was observed in subjects with at least one APOE*E4 allele (OR=3.99, 95% CI=1.97–8.08). No significant differences for the genotype distribution or the allele frequency were revealed comparing controls and patients for ACE gene. Gene-gene interaction analysis showed increase of the risk to develop AD in subjects carrying both the ACE DD genotype and the APOE*E4 allele (OR=10.32, 95% C.I. 2.67–39.81).