Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus.

BACKGROUND: Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single-nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection. OBJECTIVES: Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF. MATERIALS AND METHODS: We integrated data from the lncRNA SNP database with genome-wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression. RESULTS: The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10-6 ), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA-lncRNA interactions. CONCLUSIONS: We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.

Interactions between lifestyle and MTHFR polymorphisms on homocysteine concentrations in young adults belonging to the 1982 Pelotas Birth Cohort.

BACKGROUND/OBJECTIVES: Homocysteine (Hcy) is a key intermediate in methionine metabolism. A high plasma concentration of Hcy is an independent risk factor for cardiovascular diseases among other determinants. In this study, we aimed to investigate the interactions between methylenetetrahydrofolate reductase enzyme gene (MTHFR) polymorphisms and lifestyle variables (smoking, alcohol intake and physical activity) on Hcy concentrations in a young Brazilian population. SUBJECTS/METHODS: The study population comprised 3803 individuals from the Pelotas Birth Cohort, aged 22-23 years. Allelic discrimination assays and chemiluminescence immunoassays were performed for genotyping and serum Hcy measurements, respectively. Linear regression models were used to explore the effect of gene-lifestyle interactions on Hcy concentrations. RESULTS: Men carrying the MTHFR 677TT genotype, who were also smokers and drinkers (⩾15 g of alcohol per day), had the highest concentration of Hcy (P-value for the interaction <0.001 for smoking and 0.002 for alcohol intake). In contrast, high folate concentrations attenuated the effects of the MTHFR C677T genotype on serum Hcy concentrations (P-value for interaction <0.001). Also, among males, blood folate concentration was the only lifestyle variable able to modify the influence of MTHFR A1298C genotypes on Hcy concentrations (P-value for the interaction <0.001). There was no strong evidence of an interaction between the MTHFR genotypes and the lifestyle variables in women. CONCLUSIONS: In summary, our study demonstrates a sex difference in Hcy concentrations among Brazilian young adults regarding MTHFR C677T-lifestyle interactions that are worsened under conditions of low blood folate. Identification of potentially modifiable factors related to an increase in homocysteine in young adults, especially in those who are genetically susceptible, is important to prevent negative health consequences in the future.

Childhood stunting and the metabolic syndrome components in young adults from a Brazilian birth cohort study.

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the association between stunting in the second year of life and metabolic syndrome components in early adulthood among subjects who have been prospectively followed-up since birth, in a city in Southern Brazil. SUBJECTS/METHODS: In 1984, we attempted to follow-up the entire cohort; the subjects were examined and their mothers interviewed. Stunting was defined by a length-for-age Z-score 2 s.d. or more below the mean, in accordance with the World Health Organization reference. Between 2004 and 2005, we again tried to follow the entire cohort; during this period the subjects were evaluated for the following metabolic syndrome components: high-density lipoprotein (HDL) cholesterol, triglycerides, random blood glucose, waist circumference and systolic and diastolic blood pressure. Family income at the time of the baby's birth, asset index, mother's education, mother's smoking during pregnancy and duration of breastfeeding were considered possible confounders. Linear regression was used in the unadjusted and adjusted analyses. RESULTS: Among men, stunting was inversely associated with triglycerides (ß=-11.90, confidence interval (CI)=-22.33 to -1.48) and waist circumference (ß=-4.29, CI=-5.62 to -2.97), whereas for women stunting was negatively related to HDL-cholesterol (ß=-4.50, CI=-6.47 to -2.52), triglycerides (ß=-9.61, CI=-17.66 to -1.56) and waist circumference (ß=-1.14, CI=-4.22 to -1.02). However, after controlling for confounding variables, these associations vanished. CONCLUSIONS: The findings suggest that stunting in childhood is not associated with metabolic syndrome components in young adults.

Intrauterine exposure to smoking and wheezing in adolescence: the 1993 Pelotas Birth Cohort.

Previous studies have suggested an association between maternal smoking during pregnancy and asthma symptoms such as wheezing during childhood. However, few have evaluated this association in adolescence, especially in populations with high prevalence of wheezing as in Brazil. Using the 1993 Pelotas birth cohort, a longitudinal study set in southern Brazil of 5249 urban live births, we aimed to evaluate the association between maternal and the partner's smoking during pregnancy and wheezing at 11 and 15 years of age. We evaluated smoking during pregnancy using number of cigarettes/day, and our main outcomes were as follows: wheezing in the last year and number of wheezing crises, at both 11 and 15 years of age, as well as persistent wheezing (having crises at 11 and 15 years of age) and medical asthma diagnosis at age 15. In addition, other socio-demographic variables were included as possible confounders and mediators of this association. We used Poisson regression models to evaluate crude and adjusted associations. Of the 5249 live births in 1993, 87.5% and 85.7% were followed-up to 11 and 15 years of age, respectively. Maternal smoking during pregnancy showed a dose-response association with number of wheezing crises at age 15 (P = 0.023), presence of persistent wheezing (P = 0.034) and asthma diagnosis (P = 0.023). Partner's smoking was not associated with any wheezing variables. Maternal smoking during pregnancy appears to exert an effect on respiratory morbidity of adolescents, evaluated by wheezing symptoms.

Haplotype TGTG from SNP 45T/G and 276G/T of the adiponectin gene contributes to risk of polycystic ovary syndrome.

BACKGROUND: Haplotypes of adiponectin gene single nucleotide polymorphisms (SNP) might be related to metabolic disorders. AIM: To assess whether the prevalence of SNP 45T/G and 276G/T of the adiponectin gene and their haplotypes differ between polycystic ovary syndrome (PCOS) and non-hirsute cycling controls and to investigate the relationship between these haplotypes and risk factors for cardiovascular disease. SUBJECTS AND METHODS: In this case-control study, 80 women with PCOS and 1500 non-hirsute controls with regular cycles underwent clinical and laboratory measurements. Genotype distribution was analyzed by conventional PCR-restriction fragment length polymorphism. RESULTS: Compared to controls, PCOS women had greater body mass index (BMI) (31.0±7.9 kg/m² vs 23.4±4.6 kg/m²; p<0.001), waist circumference (92.2±18.8 cm vs 74.5±10.2 cm; p<0.001), and systolic and diastolic blood pressure (124.6±19.9 vs 111.5±13.0 mmHg and 79.2±12.5 vs 71.8±10.6 mmHg; p<0.025), as well as a worse lipid profile (p<0.007), even after adjustment for age and BMI. Genotype distribution was similar in PCOS and controls (45T/G: p=0.399; 276G/T: p=0.135). Six haplotypes were inferred and their frequencies differed significantly between the groups (p=0.001). The TGTG haplotype was more frequent in PCOS than controls (41.3 vs 18.9%). In PCOS, the GG genotype for SNP 276 (p=0.031) and the TGTG haplotype (p=0.023) were associated with higher systolic blood pressure vs other genotypes and haplotypes. Body composition, glucose, insulin, and lipid profile were similar across genotypes and haplotypes in both groups. CONCLUSIONS: Haplotype TGTG from adiponectin gene variants 45T/G and 276G/T is related to susceptibility to PCOS, and might be associated with increased blood pressure in PCOS.

[Smoking among teenagers in an urban area in Southern Brazil]. / Tabagismo em adolescentes de área urbana na região Sul do Brasil.

OBJECTIVE: To evaluate the prevalence of tobacco smoking and its determinants among adolescents. METHODS: A cross-sectional study, using a multiple stage sampling, was carried out in 1997 and a sample of adolescents aged between 12 and 18 years who were living in the urban area of Pelotas, Brazil, was studied. Those who reported having smoked at least one cigarette per week during the last month were considered smokers. Chi-square test was used to compare proportions and conditional logistic regression was applied in the multivariate analysis. RESULTS/ CONCLUSIONS: Six hundred and thirty-two adolescents were interviewed, among which 38 were non-respondents. Of those interviewed, 11.1% were smokers at time of the study, 6.8% were former smokers and 82.1% had never smoked. Prevalence of tobacco smoking was directly related to the age. Even after adjusting for confounding factors, those who had left or failed at school, their parents were divorced or reported alcohol abuse in the last month showed a higher odds ratio for smoking.

Maternal smoking and the risk of early weaning: a meta-analysis.

OBJECTIVES: This study reviewed evidence on the effect of maternal smoking on early weaning. METHODS: The following databases and journals were searched: Medline, Scientific Citation Index, Pediatrics, Journal of Pediatrics, New England Journal of Medicine, and Lancet. Analysis was restricted to studies in which infants who had never been breastfed were excluded or the prevalence of breastfeeding initiation was more than 90%. RESULTS: In smoking vs nonsmoking mothers, the random effects odds ratio for weaning before 3 months was 1.93 (95% confidence interval [CI] = 1.55, 2.40). An adjusted odds ratio of 1.50 (95% CI = 1.34, 1.68) was shown in studies that had lost-to-follow-up rates below 15% and included adequate adjustment for confounding. CONCLUSIONS: Maternal smoking increases the risk of early weaning.

Breast feeding, pacifier use and infant development at 12 months of age: a birth cohort study in Brazil.

Many studies suggest that breast feeding confers developmental and intellectual advantages on children. In a recent study, however, no association was found between breast feeding and intelligence in adult life after adjustment for other variables, and the use of pacifier in infancy was the most important predictor of intelligence. We analysed the associations between breast-feeding duration, pacifier use and suspected developmental delay at 12 months of age in a birth cohort in Pelotas, southern Brazil. All 5304 hospital births occurring during 1993 were studied and a sample was followed up at 1, 3, 6 and 12 months of age. Breast-feeding practices and use of pacifiers were assessed at each visit, as well as suspected developmental delay, measured by the Denver II test. The prevalence of developmental delay was analysed, through logistic regression, according to breast-feeding status and pacifier use, accounting for the possible confounding effect of other variables. The prevalence of suspected developmental delay at 12 months was 34.1%, being slightly higher among children who used pacifiers at 6 months than among non-users (35.3% and 28.7% respectively). There was a marked negative association between breast-feeding duration and developmental delay, with children breast fed for 9 months or more presenting significantly less suspected developmental delay (25.5%) than those breast fed for less than 1 month (42.4%). The effects of multiple variables were tested, and only high parity, smoking during pregnancy, birthweight, gestational age, pacifier use and breast-feeding duration remained significantly associated with suspected developmental delay. The effect of pacifier use, however, disappeared after adjusting for breast-feeding duration, suggesting that breast feeding, and not pacifiers, affects child development.

Environmental tobacco smoke and breastfeeding duration.

The effect of smoking on breastfeeding duration was investigated in a population-based birth cohort study of 1,098 Brazilian infants. There were few losses to follow-up (3.2%) in the first 6 months. Maternal smoking was strongly associated with breastfeeding duration, even after adjustment for confounding. Compared with nonsmokers, mothers smoking 20 or more cigarettes daily presented an odds ratio of 1.94 for breastfeeding for less than 6 months. Environmental tobacco smoke was also an independent risk factor. After adjustment for maternal smoking and other confounders, households where more than 10 cigarettes were smoked daily by persons other than the mother presented an odds ratio of 1.48 compared with those without smokers. These results remained unchanged after stratification for maternal smoking. This is the first report of a possible effect of environmental tobacco smoke on breastfeeding duration.

[Tobacco smoking among pregnant women in an urban area in southern Brazil, 1982-93]. / Tabagismo em gestantes de área urbana da região Sul do Brasil, 1982 e 1993.

OBJECTIVE: A comparison between on the prevalence of smoking during pregnancy in 1982 and that in 1993 in Pelotas, Southern Brazil. METHODOLOGY: Cross-sectional study. All hospital deliveries in 1982 and 1993--corresponding to over 99% of all births in those years--were studied. A total of 6,011 and 5,304 mothers were interviewed, respectively. RESULTS: The prevalence of smoking during pregnancy showed a small decrease from 35.7% in 1982 to 33.5% in 1993 (p < 0.05). In the two years under study, family income and number of antenatal care visits were inversely associated with the prevalence of maternal smoking. The rate of stopping smoking during pregnancy was 20.6%.

Low birthweight, preterm births and intrauterine growth retardation in relation to maternal smoking.

The association between the intensity and duration of cigarette smoking during pregnancy and the frequency of low birthweight, preterm births and intrauterine growth retardation was investigated in a historical cohort. All 5166 livebirths occurring in the city of Pelotas, Brazil, during 1993 were identified and mothers interviewed soon after delivery. Children whose mothers smoked during pregnancy had a birthweight 142 g lower than those of non-smoking mothers. The odds ratio for low birthweight among children of smokers was 1.59 [95% CI 1.30-1.95]. There was no association between smoking and preterm delivery assessed by the Dubowitz score. In relation to intrauterine growth retardation, smoking was associated with an odds ratio of 2.07 [95% CI 1.69-2.53]. There was a direct dose-response association between the number of cigarettes smoked and the risk of growth retardation. Women whose partner smoked were also at higher risk of having a child with growth retardation. All the above results were adjusted for confounding factors. The effect of maternal smoking on low birthweight seems to be attributable to intrauterine growth retardation rather than preterm delivery.

PIP: Although the deleterious effect of maternal smoking on birth weight has been well documented, no study has investigated the impact of smoking on the different combinations of low birth weight (LBW), preterm delivery, and intrauterine growth retardation (IUGR). The present study addressed these associations through a cohort analysis of virtually all 5166 live births occurring in Pelotas, Brazil, in 1993. Mean birth weight was 3169 g; the prevalences of LBW, preterm birth, and IUGR were 9.1%, 8.0%, and 8.9%, respectively. The prevalence of smoking at conception was 33.2%; 26.2% of mothers smoked during the entire pregnancy; and 43% of mothers' partners smoked. The infants of mothers who smoked during pregnancy weighed an average of 142 g less at birth than those of nonsmokers. Logistic regression analyses of LBW were adjusted for social class, maternal education, parity, pregnancy interval, prior LBW, maternal height, and number of antenatal care visits. Mothers who smoked for part or all of the pregnancy were 1.59 times more likely to deliver a LBW infant than nonsmokers. There was no association between maternal smoking and preterm delivery. The risk of IUGR was 2.07 times higher in mothers who smoked; women who stopped smoking during the first trimester, however, had a risk similar to that of nonsmokers. Smoking by the mother's partner also increased the risk of IUGR (odds ratio, 1.33). Smoking was associated with at least a doubling of risk of IUGR, whether or not LBW or preterm birth was also present, suggesting that IUGR is the key factor mediating the effect of smoking on birth weight.

Benzodiazepínicos: estudo de prescriçäo em um posto de atençäo primária à saúde / Benzodiazepinics: prescription study in a primary health care unit

OBJETIVO. Estudar a taxa de prescriçäo de benzodiazepínicos em um posto de Atençäo Primária à Saúde na cidade de Pelotas, RS. MÉTODOS. Foram registradas as consultas realizadas num período de 12 meses, como também as drogas prescritas. Para fins de análise de prescriçäo de benzodiazepínicos, somente as 3.368 consultas dos pacientes com idade superior a 25 anos foram consideradas. RESULTADOS. Os pacientes na faixa etária de 45-64 anos, de ambos os sexos, foram aqueles que apresentaram uma maior taxa de prescriçäo, sendo essa a terceira droga mais prescrita para os homens e a quarta para as mulheres. CONCLUSäO. Os resultados demonstram que os benzodiazepínicos encontram-se entre as drogas mais prescritas

[Smoking habits among students at the Pelotas Medical School: prevalence in 1986 and 1991]. / Hábito de fumar entre estudantes de medicina da Universidade Federal de Pelotas, Brasil: comparação entre as prevalências de 1986 e 1991.

A cross-sectional survey of smoking habits was carried out among students at the School of Medicine in Pelotas, State of Rio Grande do Sul, Brazil, in 1986 and 1991. The overall participation rate for the originally selected sample was 96% and 98% respectively. In 1986, regular smokers comprised 21.6% of the students and 14.6% in 1991; former smokers were 7.3% and 10.9%, respectively. There was no association between sex, parental smoking, and smoking habits of the students. Students in their last two years of medical training showed an increased prevalence in smoking habits (1991). Respiratory symptoms were associated with smoking habits. It was concluded that the prevalence of smoking is decreasing among students of the School of Medicine in Pelotas.

[Determinants of the smoking habit in the city of Pelotas, Brazil]. / Determinantes do hábito de fumar na cidade de Pelotas, Brasil.

Although the harmful effects of smoking on health are well documented, this habit continues to be highly prevalent in Latin America. The objective of this study is to evaluate the frequency of this habit and its possible determinants in the adult population of the city of Pelotas, state of Rio Grande do Sul, Brazil, using a simplified methodology. With the use of a cross-sectional design, a probabilistic sample of 1,401 adults was studied; the no-response rate was 11%. Of those interviewed, 54% had never smoked, 14% were former smokers, and 33% were smokers at the time of the study; 16% smoked 20 or more cigarettes daily. Smoking was more frequent in men (44%) than in women (23%). In relation to educational level, the highest prevalence of smoking was among individuals with five to eight years of schooling (39.7%). The study showed that it is possible with a limited investment of time and resources, to evaluate the frequency of smoking in a representative sample of a medium-sized city, yielding data that will be highly useful for preventive campaigns.

Patterns of maté drinking in a Brazilian city.

Maté drinking, a hot infusion of Ilex paraguayensis commonly drunk in parts of South America, has been associated with increased risks of upper digestive cancers. In a population-based survey, we have studied the patterns of maté drinking in a sample of 1400 adults living in a southern Brazilian city. Approximately one third of the population drank maté less than once a month or not at all; another third drank maté at least once a month, but less than once a day; while the remaining third drank maté daily. Daily drinking was most common among individuals aged under 60, those who migrated from rural areas, and among cigarette smokers. Drinkers ingested on average about 1800 ml/day at a mean temperature of 69.5 degrees C. Individuals who had never attended school tended to ingest larger quantities. The temperature of the drink was higher for males and for drinkers of alcoholic beverages. This information may contribute to the design of preventive interventions, since a large proportion of upper digestive cancer cases in those regions might be due to maté drinking.