Sex-specific effect of the thermolabile C677T mutation in the methylenetetrahydrofolate reductase gene on angiographically assessed coronary artery disease in Brazilians

Hyperhomocysteinemia is associated with increased coronary artery disease (CAD) risk. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine and presents a common mutation (C677T) that leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased CAD risk. The C677T MTHFR mutation was studied in 772 subjects (480 Caucasian Brazilians and 292 African Brazilians) who underwent coronary angiography at the hemodynamic center of the Santa Izabel Hospital in Salvador, Bahia State, Brazil. The 677T allele frequency was increased in Caucasian Brazilians (28.1%) compared to the frequency observed in African Brazilians (18.3%; p < 0.001). In Caucasian Brazilians the frequency of the 677T homozygous genotype was increased in CAD cases (10.4%) compared to control subjects (1.4%; p = 0.014) in males but not in females. In African Brazilians the mutation was not associated with CAD in either sex. The multivariate logistic regression analysis of all the samples shows that the 677T homozygous interaction with sex was a significant CAD predictor, independent of other classical risk factors and ethnic group. The odds ratio associated with male 677T homozygotes was increased 9.2-fold (p = 0.021) compared to the 677C carriers. The present study suggests that the C677T MTHFR mutation is associated with increased CAD risk in a sex-dependent manner in Brazilians.     

Prevalence of cytomegalovirus antibodies in Brazilian and Japanese populations in the north-east of Brazil

The serological status to cytomegalovirus (CMV) was examined for 616 Brazilians and 399 Japanese immigrants living in the North-East of Brazil. The sera were screened for IgG antibodies to CMV by enzyme-linked immunosorbent assay (ELISA). The overall prevalence of CMV antibodies was higher in the Japanese population (83.7%) than in the Brazilian population (69.8%). The seropositivity was analyzed by factors of age, sex, ethnic background, and socioeconomic status. Mother-baby contact seems to be a factor of significance in the seroepidemiology of CMV infection.     

Factors associated with longitudinal plasma selenium decline in the elderly: the EVA study

Selenium status decreases in elderly populations. Cardiovascular diseases are the primary cause of death in the French elderly, and selenium may protect against cardiovascular diseases. The present work aims to evaluate the relationships between cardiovascular-related risk factors and plasma selenium variability in an elderly population during a 9-year period. Seven hundred fifty-one subjects from the EVA ("Etude du Vieillissement Artériel") study, aged 59 to 71 at baseline, were followed for 9 years. Clinical examinations and lifestyle questionnaires were repeated every 2 years. Plasma selenium determinations were performed at baseline and at the end of the study. The association between the 9-year plasma selenium variability and studied risk factors at baseline or occurring during the follow-up was evaluated by using multivariate linear regression models. After controlling all potential associated factors, age of subjects (P<.01), obesity (P=.02) and occurrence of cardiovascular disease during follow-up (P=.03) increased the longitudinal decline in plasma selenium, whereas gender, education, smoking, alcohol intakes, dyslipidemia, diabetes, hypertension had no effect (P>.05). It may be postulated that obesity and occurrence of cardiovascular events are the main factors associated with plasma selenium fall during ageing. The respective roles played by nutritional and metabolism changes in the mechanism of these associations still need to be explored.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Y Chromosome Diversity in Brazilians: Switching Perspectives from Slow to Fast Evolving Markers

We have previously shown that the Y chromosomes of ‘white’ Brazilians have their immediate geographical origin in Europe, with low frequency of sub-Saharan African chromosomes and virtual absence of Amerindian contribution. The typing of slow evolving polymorphisms on the Y chromosome also revealed no differences between Brazilians and Portuguese, the bulk of European immigrants to Brazil, and even among Brazilians from distinct regions of Brazil, the latter being in sharp contrast with mtDNA data. In order to test if the lack of differentiation is a sex-biased and not a marker-biased phenomenon, we decided to study faster evolving Y chromosome markers in samples from Brazil and Portugal previously studied. The population structure revealed by this work confirmed that there were indeed no significant differences between Brazil and Portugal and no population differentiation within the four geographical regions of Brazil, suggesting that this phenomenon is unrelated to the nature of the markers typed. Nevertheless the fast evolving markers did uncover a higher within population diversity in Brazil than Portugal, which could be explained by the input of diverse European Y chromosomes carried by several migration waves to Brazil. Our present data highlight the significance of typing and combining Y markers that evolve according to distinct mutational paces to usefully assess the levels of diversity in a given population, and can be applied in the study of populations derived from distinct geographical origins such as the Brazilians.     

Analysis of Apolipoprotein E gene polymorphism in populations of the Volgo-Ural region]

Polymorphism at the apolipoprotein E gene (ApoE) in populations of the Volga-Ural region was studied by means of polymerase chain reaction. In the region examined the population-specific patterns of the ApoE alleles and genotypes frequency distribution were established. The results obtained were compared with the literature data on the ApoE polymorphism in other world populations. Substantial heterogeneity of different ethnic populations in respect to the ApoE genotypes distribution and frequency was revealed.     

Number of teeth and selected cardiovascular risk factors among elderly people

doi:10.1111/j.1741‐2358.2009.00328.x
Number of teeth and selected cardiovascular risk factors among elderly people Objective: To produce evidence on an association between the number of teeth and selected cardiovascular risk factors among an elderly population. Materials and methods: The study population comprised of 523 community‐living elderly people who participated in the population‐based Kuopio 75+ study. The data for each subject were collected using a structured clinical health examination, an interview and laboratory tests. Linear regression models were used to estimate adjusted mean values and confidence limits. Results: Edentulous persons and persons with a small number of teeth had lower serum HDL cholesterol and higher triglyceride, leucocyte and blood glucose levels and a higher body mass index (BMI) compared with subjects to a large number of teeth. Conclusion: The study showed that, in the Finnish home‐dwelling population aged 75 years or older, those with a large number of teeth were less likely to have cardiovascular risk factors such as a low serum HDL cholesterol level, a high triglyceride level and a high BMI than did subjects with a small number of teeth or who were edentulous.     

High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 1,000 different mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). To determine the frequency of 70 common worldwide CFTR mutations in 155 Euro-Brazilian CF patients and in 38 Afro-Brazilian CF patients, we used direct PCR amplification of DNA from a total of 386 chromosomes from CF patients born in three different states of Brazil. The results show that screening for seventy mutations accounts for 81% of the CF alleles in Euro-Brazilians, but only 21% in the Afro-Brazilian group. We found 21 different mutations in Euro-Brazilians and only 7 mutations in Afro-Brazilians. The frequency of mutations and the number of different mutations detected in Euro-Brazilians are different from Northern European and North American populations, but similar to Southern European populations; in Afro-Brazilians, the mix of CF-mutations is different from those reported in Afro-American CF patients. We also found significant differences in detection rates between Euro-Brazilian (75%) and Afro-Brazilian CF patients (21%) living in the same state, Minas Gerais. These results, therefore, have implications for the use of DNA-based tests for risk assessment in heterogeneous populations like the Brazilians. Further studies are needed to identify the remaining CF mutations in the different populations and regions of Brazil.     

Association of ACE I/D polymorphism with cardiovascular risk factors

Since the identification of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene, the D allele has been recognized to be associated with cardiovascular disease. Moreover, significant associations of this polymorphism with multiple cardiovascular risk factors have been reported, although some studies failed to detect such associations. In the present study, we investigated the association of the ACE gene polymorphism with the parameters of multiple risk factors in 300 Japanese men who participated in a medical check-up. This investigation detected a significant association of the polymorphism with systolic blood pressure (P=0.007) and diastolic blood pressure (P=0.026), with their highest values in DD subjects and lowest values in II subjects. This significant association is consistent with the proposition that the polymorphism influences blood-pressure variability in men. Furthermore, we investigated the association of the polymorphism with four major disorders (obesity, hyperlipidemia, hypertension, diabetes mellitus) correlated with the risk for cardiovascular disease in the same 300 subjects. This investigation failed to detect any significant association of the polymorphism with each disorder. However, there was a trend that all four disorders were more frequent in ID and DD subjects than in II subjects. We therefore analyzed the association between the ACE gene polymorphism and having at least one of the four disorders in the same population. This analysis detected a significant difference: that ID and DD subjects had at least one of the four disorders more frequently than II subjects (P=0.008; odds ratio=1.89, 95% confidence interval= 1.19-2.99). Taken together, the results of this study are compatible with the proposition that the ACE polymorphism is associated with cardiovascular disease partially mediated through the four disorders in our population.     

Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study

Pathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification. This cross-sectional study evaluated the relationship between physiological levels of urinary phytate and heart valve calcification in a population of elderly out subjects. A population of 188 elderly subjects (mean age: 68 years) was studied. Valve calcification was measured by echocardiography. Phytate determination was performed from a urine sample and data on blood chemistry, end-systolic volume, concomitant diseases, cardiovascular risk factors, medication usage and food were obtained. The study population was classified in three tertiles according to level of urinary phytate: low (<0.610 μM), intermediate (0.61–1.21 μM), and high (>1.21 μM). Subjects with higher levels of urinary phytate had less mitral annulus calcification and were less likely to have diabetes and hypercholesterolemia. In the multivariate analysis, age, serum phosphorous, leukocytes total count and urinary phytate excretion appeared as independent factors predictive of presence of mitral annulus calcification. There was an inverse correlation between urinary phytate content and mitral annulus calcification in our population of elderly out subjects. These results suggest that consumption of phytate-rich foods may help to prevent cardiovascular calcification evolution.     

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations

Apolipoprotein E (apoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess whether apoE is a genetic risk factor for cholesterol gallstone disease (GD), we analyzed apoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. ApoE genotypes were determined in Chilean gallstone patients (n = 117) and control subjects (n = 122) as well as in German gallstone patients (n = 184) and matched controls (n = 184). In addition, we studied apoE variants in subgroups of Chilean patients with strong differences in their susceptibility to acquire gallstones: 50 elderly subjects without gallstones in spite of well-known risk factors for this disease (gallstone-resistant) and 32 young individuals with gallstones but without risk factors (gallstone-susceptible). Furthermore, correlation analysis of apoE genotypes with cholesterol crystal formation times, biliary cholesterol saturation index (CSI), and gallstone cholesterol contents was performed in 81 cholecystectomized patients. In this study analyzing the largest sample set available, apoE4 genotype was not associated with an increased frequency of GD in either population. Moreover, in the Chilean population after adjusting for risk factors such as gender, age, body mass index, serum lipids, and glucose, the odds ratio for the association of the apoE4 allele and GD was significantly (P < 0.05) <1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. In contrast to previous smaller studies, apoE polymorphisms were not associated with susceptibility to cholesterol GD in high-risk populations.     

ApoE −491A/T Promoter Polymorphism is not an Independent Risk Factor,but Associated with the ε4 Allele in Hungarian Alzheimer’s Dementia Population

Apolipoprotein E gene (Apoε) has three common alleles (ε2, ε3, and ε4), of which ε4 has been shown to be associated with an increased risk for Alzheimer’s disease (AD). Possible additional genetic factors, like the −491A variant of ApoE promoter may modify the development of AD, independently of the ApoE allele status. The objective of this study was to investigate whether A/T allelic polymorphism at site−491 of the ApoE promoter is associated with AD in a Hungarian population. The genomic DNA isolated from peripheral blood lymphocytes of 52 late-onset AD and 53 control individuals was used as a template for the two examined polymorphisms and PCR assay was applied. The ε4 allele was significantly over-represented in the AD group (28%) as compared with the control population (7%). No significant differences have been found between the control and the AD populations regarding the occurrence of the promoter A allele frequencies (control: 77%, AD: 70%). However, the AA genotype was more frequent in the AD group (48%) than in the control (10%) when the presence of ε4 allele was also considered. It is unlikely therefore that the −491A variant of the ApoE promoter gene is an independent risk factor in the Hungarian AD population, but a linkage disequilibrium exists between the two examined mutations.     

High frequency of CYP1A1*2C allele in Brazilian populations

The genetic variability of the CYP1A1 I462V polymorphism (CYP1A1*2C) was investigated in four Brazilian populations: three groups of African descent and one group of European descent. The CYP1A1 polymorphism was analyzed by two different procedures, first by the allele-specific polymerase chain reaction (PCR) method and then by the PCR-restricted fragment length polymorphism (PCR-RFLP) method before digestion with BsrDI. The frequency of CYP1A1 *2C was 11% in Brazilians of European descent, a frequency that is slightly higher but not statistically different from that observed in European populations. In Brazilians of African ancestry this value was very high (12% to 15%). This allele was not observed in the only two African populations investigated thus far. By themselves, the two factors of interethnic admixture (with populations of European descent and/or Amerindian populations) and genetic drift cannot explain the high values observed here. Our findings suggest that the CYP1A1 *2C allele may possibly be present in Africa, but restricted to some ethnic groups not yet investigated. Environmental factors in South America might also have acted as selective factors increasing the CYP1A1 *2C gene frequency. Our data also suggest that the CYP1A1 *2C allele might possibly have originated in Africa.     

Association among oxidized LDL levels, MnSOD, apolipoprotein E polymorphisms, and cardiovascular risk factors in a south Brazilian region population

Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.     

Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification.     

Factors associated with missing teeth in the Brazilian elderly institutionalised population

doi:10.1111/j.1741‐2358.2012.00655.x Factors associated with missing teeth in the Brazilian elderly institutionalised population Objective: Identify factors associated with missing teeth in the elderly institutionalised population in Brazil. Methodology: Cross‐sectional study of elderly institutionalised Brazilians with 1192 subjects. A questionnaire was applied as well as an epidemiological survey of oral health conditions in accordance with WHO. Factorial analysis was carried out with variables related to missing teeth, as well as the Fisher’s exact test, chi‐squared test and multiple logistic regression. Results: Mean age was 76.3 (±9.8), 53.5% (638) of subjects were women and 717 (60.2) were dependent. Mean of Decayed Missing and Filled Teeth Index (DMFT index) was 29.4 (±4.9). The subjects that did not use upper and lower dentures were 61.5% (732) and 79.2% (944), respectively. Median number of missing teeth per person was 27.88 (±6.8) with a mean of 4 (±6.6) teeth present and 2.4 (±4.5) caries‐free teeth. Factors associated with missing teeth following multivariate analysis were: age, sex, self‐assessment of oral health, access to health services, type of institution and area of the country. Conclusions: High level of tooth loss and low level of rehabilitation demonstrate precarious oral health. It is therefore necessary to improve institutional access mechanisms to public health facilities for the institutionalised elderly.     

Genotypic analysis of Mycobacterium leprae isolates from Japan and other Asian countries reveals a global transmission pattern of leprosy

The genotype of single-nucleotide polymorphism type 3, CTC, at positions 14676, 164275, and 2935685, along with four copies of 6 bp repeats in the rpoT gene, was predominant for isolates originating in the Japanese mainland. Type 1, CGA, type 2, CTA, and type 3 were detected from Korea, Indonesia, and Myanmar. No isolates with four copies of 6 bp were detected from Myanmar, Okinawa, and Japanese Brazilian patients. Type 4, TTC, with three copies of 6 bp, was detected only from Japanese Brazilians. The results indicate that infection occurred in Brazil and the disease developed later in Japan.     

Apolipoprotein E4 and memory decline in the elderly

The objective of this study was to investigate whether the association between Apolipoprotein E4 (ApoE4) and memory decline is modified by baseline general cognitive impairment and age in a population-based elderly sample. Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The study sample consisted of 1,243 subjects, 62-85 years old, with a Mini-Mental State Examination (MMSE) score between 21-30 and known ApoE phenotypes. Memory performance was measured with a short version of the Auditory Verbal Learning Test (AVLT) at baseline and repeated after three years (N = 854). Memory decline was defined as a decrease of at least one standard deviation from the mean change score on immediate recall, delayed recall and retention. ApoE4 was associated with memory decline in cognitively impaired subjects (MMSE 21-26), but not in cognitively normal subjects (MMSE 27-30). In particular cognitively impaired E4 carriers older than 75 years were at high risk of memory decline. Contrary to AD studies, our study suggests that the risk of ApoE4 on memory decline does not decrease with ageing.     

UACR在老年人群中的分布及其与心血管病危险因素的相关性研究

目的-观察老年人群尿微量白蛋白与尿肌酐比值（UACR）的分布情况,探讨其与心血管病危险因素的相关性。方法：选取2011年5月至2012年11月在我院接受体检的年龄在60岁以上的老年人922名,收集整理上述人群的基本临床资料。通过检测其清晨尿样,分析UACR在老年人群中的分布情况及和其于心血管病危险因素的关系。结果：①问卷调查结果：在接受调查的所有老年人中,有68名为健康人群,有724名为具有不同程度的心血管病危险因素人群。78．52％的老年人存在至少1个或多个心血管病危险因素。在众多心血管病危险因素中,患病率排在前三位的是：血脂异常、高血压和糖尿病。（2）UACR检测结果：健康人群中,男性UACR显著低于女性,差异有统计学意义（P〈0．05）;患有高血压,糖尿病和血脂异常人群的UACR显著高于健康人群,差异有统计学意义（P〈0．05）。结论：尿微量白蛋白与尿肌酐比值（UACR）与老年人群心血管疾病危险因素有着密切的联系,通过检测患者的UACR,为心血管疾病的治疗及预后奠定基础。     

The relationship between genetic polymorphisms in apolipoprotein E (ApoE) gene and osteonecrosis of the femoral head induced by steroid in Chinese Han population

Previous studies suggested that apolipoprotein E (ApoE) genetic polymorphisms (SNPs) may result in abnormal lipid metabolism. Therefore, genetic polymorphisms in ApoE may be associated with the occurrence of osteonecrosis of the femoral head (ONFH). A case control study was designed to include 580 patients with steroid-induced ONFH and 560 age- and sex-matched non steroid-induced ONFH control subjects to analyze the association between ApoE polymorphisms and susceptibility of steroid-induced ONFH. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to differentiate two genotypes SNPs (rs7412 C/T and rs429358 T/C) in ApoE gene. Both rs7412 C/T and rs429358 T/C were found to be associated with the risk of steroid-induced ONFH. However, no significant association was observed between the haplotypes T-T, T-C and C-C in ONFH. Furthermore, T allele of rs7412 and C allele of rs429358 carriers were associated with higher levels of TG in steroid-induced ONFH patients (P?<?0.05). The study suggested that ApoE genetic polymorphisms conferred susceptibility to steroid-induced ONFH in Chinese Han population. However, the results need further investigation with large sample size and various populations.