Genetic Contribution for Non-Syndromic Cleft Lip With or Without Cleft Palate (NS CL/P) in Different Regions of Brazil and Implications for Association Studies

Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarem, Fortaleza, Barbalha, Maceio, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarem (44%) and the lowest in Maceio (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarem (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceio (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceio to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies. (C) 2011 Wiley-Liss, Inc.

The shoot controls zeatin riboside export from pea roots. Evidence from the branching mutant rms4

The rms4 mutant of pea (Pisum sativum L.) was used in grafting studies and cytokinin analyses of the root xylem sap to provide evidence that, at least for pea, the shoot can modify the import of cytokinins from the root. The rms4 mutation, which confers a phenotype with increased branching in the shoot, causes a very substantial decrease (down to 40-fold less) in the concentration of zeatin riboside (ZR) in the xylem sap of the roots. Results from grafts between wild-type (WT) and rms4 plants indicate that the concentration of cytokinins in the xylem sap of the roots is determined almost entirely by the genotype of the shoot. WT scions normalize the cytokinin concentration in the sap of rms4 mutant roots, whereas mutant scions cause WT roots to behave like those of self-grafted mutant plants. The mechanism whereby rms4 shoots of pea cause a down-regulation in the export of cytokinins from the roots is unknown at this time. However, our data provide evidence that the shoot transmits a signal to the roots and thereby controls processes involved in the regulation of cytokinin biosynthesis in the root.

Age-dependent increase in blood pressure in two different Native American communities in Brazil

Objective Cardiovascular risk factors were surveyed in two Indian populations (Guarani, n=60; Tupinikin, n=496) and in a non-Indian group (n=114) living in the same reserve in southeast Brazilian coast. The relationship between an age-dependent blood pressure (BP) increase with salt consumption was also investigated. Methods Overnight (12 h) urine was collected to evaluate Na excretion. Fasting glucose and lipids, anthropometry, BP, ECG and carotid-femoral pulse wave velocity (PWV) were measured in a clinic visit. Participation (318 men/352 women, age 20-94 years; mean=37.6 +/- 14.9 years) comprised 80% of the eligible population. Results The prevalence of hypertension, diabetes and high cholesterol was similar in Tupinikins and in non-Indians and higher than in Guaranis. The prevalence of smoking and obesity was higher in the latter group. Hypertension and diabetes were detected in only one individual of the Guarani group. Mean BP adjusted to age and BMI was significantly lower (P<0.01) in Guaranis (82.8 +/- 1.6 mmHg) than in Tupinikins (92.3 +/- 0.5 mmHg) and non-Indians (91.6 +/- 1.1 mmHg). Urinary Na excretion (mEq/12h), however, was similar in the three groups (Guarani=94 +/- 40; Tupinikin=105 +/- 56; non-Indian=109 +/- 55; P>0.05). PWV (m/s) was lower (P<0.01) in Guarani (7.5 +/- 1.4) than in Tupinikins (8.8 +/- 2.2) and non-Indians (8.4 +/- 2.0). Multiple regression analysis showed that age and waist-to-hip ratio (WHR) were independent predictors of SBP and DBP (r(2)=0.44) in Tupinikins, whereas the WHR was the unique independent predictor of BP variability in Guaranis (r(2)=0.22). Conclusion Lower BP levels in Guaranis cannot be explained by low salt intake observed in other primitive populations. J Hypertens 27:1753-1760 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Better CD4+T Cell Recovery in Brazilian HIV-Infected Individuals Under HAART Due to Cumulative Carriage of SDF-1-3`A, CCR2-V64I, CCR5-D32 and CCR5-Promoter 59029A/G Polymorphisms

Polymorphisms of chemokines and chemokine-receptors genes have been shown to influence the rate of progression to AIDS; however, their influence on response to HAART remains unclear. We investigated the frequency of the SDF-1-3`A, CCR2-64I, CCR5-D32 and CCR5-Promoter-59029-A/G polymorphisms in Brazilian HIV-1-infected and uninfected individuals and their influence on CD4+ T-cell evolution HIV-1 infected individuals before and during HAART. Polymorphism detection was done in a transversal study of 200 HIV-1-infected and 82 uninfected individuals. The rate of CD4+ T cell increase or decrease was studied in a cohort of 155 HIV-1 infected individuals on pre and post-HAART. Polymorphisms were determined by PCR associated with RFLP. The rate of CD4+ T-cell decline or increase was also determined. HIV-1 infected and uninfected subjects showed, respectively, frequencies of 0.193 and 0.220 for SDF-1-3`A, of 0.140 and 0.110 for CCR2-V64I, of 0.038 and 0.055 for CCR5-D32, and of 0.442 and 0.390 for CCR5-P-59029-A/G. HIV-1-infected subjects carrying one, two or three of these four polymorphisms showed better CD4+ T-cell recovery than HIV-1-infected subjects carrying the four wild-type alleles (+2.7, +1.6, +3.5, and -0.9 lymphocytes/mu l/month, respectively). Regression logistic analysis showed that the CCR5-D32/CCR2-V64I association was predictor of positive CD4+ T cell slope after HAART. The distribution of polymorphisms did not differ between HIV-1-infected and uninfected individuals, but differed from more homogenous ethnic groups probably reflecting the miscegenation of the Brazilian population. We add further evidence of the role of these polymorphisms by showing that the CD4 gain was influenced by carriage of one or more of the polymorphisms studied here. These results highlight the possibility that these genetic traits can be useful to identify patients at risk for faster progression to AIDS or therapeutic failure.

Resting energy expenditure in white and non-white severely obese women

This study aimed to compare the resting energy expenditure (REE) of white and non-white severely obese Brazilian women. REE was examined in 83 severely obese Brazilian women (n = 58 white and 25 non-white) with mean (+/- SD) age 42.99 +/- 11.35 and body mass index 46.88 +/- 6.22 kg/m(2) who were candidates for gastric bypass surgery. Body composition was assessed by air displacement plethysmography (ADP) BOD PODO body composition system (Life Measurement Instruments, Concord, CA) and REE was measured, under established protocol, with an open-circuit calorimeter (Deltatrac II MBM-200, Datex-Ohmeda, Madison, WI, USA). There was no significant difference between the REE of white and non-white severely obese women (1,953 +/- 273 and 1,906 +/- 271 kcal/d, respectively; p = 0.48). However, when adjusted for fat free mass (MLG), REE was significantly higher in non-white severely obese women (difference between groups of 158.4 kcal, p < 0.01). REE in white women was positively and significantly correlated to C-reactive protein (PCR) (r = 0.41.8; P < 0.001) and MLG (r = 0.771; P < 0.001). In the non-white women, REE was only significantly correlated to MLG (r = 0.753; P < 0.001). The multiple linear regression analysis showed that skin color, MLG and PCR were the significant determinants of REE (R(2) = 0.55). This study showed that, after adjustment for MLG, non-white severely obese women have a higher REE than the white ones. The association of body composition inflammation factors and REE in severely obese Brazilian women remains to be further investigated.

The rms1 mutant of pea has elevated indole-3-acetic acid levels and reduced root-sap zeatin riboside content but increased branching controlled by graft-transmissible signal(s)

Rms1 is one of the series of five ramosus loci in pea (Pisum sativum L.) in which recessive mutant alleles confer increased branching at basal and aerial vegetative nodes. Shoots of the nonallelic rms1 and rms2 mutants are phenotypically similar in most respects. However, we found an up to 40-fold difference in root-sap zeatin riboside ([9R]Z) concentration between rms1 and rms2 plants. Compared with wild-type (WT) plants, the concentration of [9R]Z in rms1 root sap was very low and the concentration in rms2 root sap was slightly elevated. To our knowledge, the rms1 mutant is therefore the second ramosus mutant (rms4 being the first) to be characterized with low root-sap [9R]Z content. Like rms2, the apical bud and upper nodes of rms1 plants contain elevated indole-3-acetic acid levels compared with WT shoots. Therefore, the rms1 mutant demonstrates that high shoot auxin levels and low root-sap cytokinin levels are not necessarily correlated with increased apical dominance in pea. A graft-transmissible basis of action has been demonstrated for both mutants from reciprocal grafts between mutant and WT plants. Branching was also largely inhibited in rms1 shoots when grafted to rms2 rootstocks, but was not inhibited in rms2 shoots grafted to rms1 rootstocks. These grafting results are discussed, along with the conclusion that hormone-like signals other than auxin and cytokinin are also involved.

The personal constructs of coping with chronic low back pain: is coping a necessary evil?

The construct of coping is explored in this paper utilising repertory grid technique with a small group of non-patients with chronic pain. Nineteen volunteers with low back pain completed a repertory grid with eight given elements signifying various self and illness-related roles. Two constructs were given and the remainder elicited using the triad method. The 19 participants rated themselves as being in less pain than those they typified as ill or disabled and considered themselves to be coping with their pain. The constructs elicited emphasised authenticity, the limitations of being a coper, mastery, active stoicism, cheerfulness, acceptance and maintaining acceptable social interactions and appearances. Copers were considered to not be in constant pain. Self, ideal-self and social-self constructs were closely related, The participants rated themselves more like copers than ill, pain-suffering, invalid or hypochondriacal persons. Being a coper, however, was less desirable than being pain free, In essence, these volunteers with low back pain see coping as a necessary evil. This ambivalent and ambiguous construing of coping needs to be further explored in community and patient groups if we are to improve the collaboration between patients and therapists in achieving good pain management. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.

Establishment and characterization of androgen-independent human prostate cancer cell lines, PcBra1, PcBra2, and PcBra3

One of the main obstacles for understanding biological events involved in cancer is the lack of experimental models for in vitro studies especially for prostate cancer (PC).There are a limited number of PC cell lines being the majority originated from metastatic tumors mostly acquired from American Tissue Cell Culture which demands importation an expensive and bureaucratic process. Also it is well known that there are ethnic differences between populations concerning the behavior of tumors and the research based on cell lines derived from Brazilians should be interesting. Our aim was to develop tumor cell lines from primary PC.

VKORC1 polymorphisms in Brazilians: comparison with the Portuguese and Portuguese-speaking Africans and pharmacogenetic implications

Aims: The heterogeneity of the Brazilian population renders the extrapolation of pharmacogenomic data derived from well-defined ethnic groups inappropriate. We investigated the influence of self-reported `race/color`, geographical origin and genetic ancestry on the distribution of four VKORC1 SNPs and haplotypes in Brazilians. Comparative data were obtained from two major ancestral roots of Brazilians: Portuguese and Africans from former Portuguese colonies. Materials & methods: A total of 1037 healthy adults Brazilians, recruited at four different geographical regions and self identified as white, brown or black (race/color categories), 89 Portuguese and 216 Africans from Angola and Mozambique were genotyped for the VKORC1 3673G>A (rs9923231), 5808T>G (rs2884737), 6853G>C (rs8050894) and 9041G>A (rs7294) polymorphisms using TaqMan (R) (Applied Biosystems, CA, USA) assays. VKORC1 haplotypes were statistically inferred using the haplo.stats software. We inferred the statistical association between the distribution of the VKORC1 polymorphisms among Brazilians and self-reported color, geographical region and genetic ancestry by fitting multinomial log linear models via neural networks. Individual proportions of European and African ancestry were used to assess the impact of genetic admixture on the frequency distribution of VKORC1 polymorphisms among Brazilians, and for the comparison of Brazilians with Portuguese and Africans. Results: The frequency distribution of the 3673G>A and 5808T>G polymorphisms, and VKORC1 haplotypes among Brazilians varies across geographical regions, within self-reported color categories and according to the individual proportions of European and African genetic ancestry. Notably, the frequency of the warfarin sensitive VKORC1 3673A allele and the distribution of VKORC1 haplotypes varied continuously as the individual proportion of European ancestry increased in the entire cohort, independently of race/color categorization and geographical origin. Brazilians with more than 80% African ancestry differ significantly from Angolans and Mozambicans in frequency of the 3673G>A, 5808T>G and 6853G>C polymorphisms and haplotype distribution, whereas no such differences are observed between Brazilians with more than 90% European ancestry and Portuguese individuals. Conclusion: The diversity of the Brazilian population, evident in the distribution of VKORC1 polymorphisms, must be taken into account in the design of pharmacogenetic clinical trials and dealt with as a continuous variable. Warfarin dosing algorithms that include `race` terms defined for other populations are clearly not applicable to the heterogeneous and extensively admixed Brazilian population.

(1)H magnetic resonance spectroscopy imaging of the hippocampus in patients with panic disorder

Recent theories of panic disorder propose an extensive involvement of limbic system structures, such as the hippocampus, in the pathophysiology of this condition. Despite this, no prior study has examined exclusively the hippocampal neurochemistry in this disorder. The current study used proton magnetic resonance spectroscopy imaging ((1)H-MRSI) to examine possible abnormalities in the hippocampus in panic disorder patients. Participants comprised 25 panic patients and 18 psychiatrically healthy controls. N-acetylaspartate (NAA, a putative marker of neuronal viability) and choline (Cho, involved in the synthesis and degradation of cell membranes) levels were quantified relative to creatine (Cr, which is thought to be relatively stable among individuals and in different metabolic condition) in both right and left hippocampi. Compared with controls, panic patients demonstrated significantly lower NAA/Cr in the left hippocampus. No other difference was detected. This result is consistent with previous neuroimaging findings of hippocampal alterations in panic and provides the first neurochemical evidence suggestive of involvement of this structure in the disorder. Moreover, lower left hippocampal NAA/Cr in panic disorder may possibly reflect neuronal loss and/or neuronal metabolic dysfunction, and could be related to a deficit in evaluating ambiguous cues. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Lack of Association Between a 3 ` UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

Objective: To investigate a possible association between a 3`UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients (DSM-IV criteria) and 479 healthy controls. The primers` sequence used were: 3`UTR-Forward: 5`TGT GGT GAT GGG AAC GGC CTG AG 3` and 3`UTR-Reverse: 5`CTT CCT GGA GGT CAC GGC TCA AGG 3`. Alleles of the 3`UTR were coded according to their number of repeats: 6- repeat 320 bp (allele 6), 8- repeat 400 bp (allele 8), 9-repeat 480 bp (allele 9), 10- repeat 480 bp (allele 10), and 11- repeat 520 bp (allele 11). Results: There were no allelic (chi(2) = 2.67, 5df, p = .75) and genotypic (chi(2) = 7.20, 1df, p = .61) association between adult ADHD and VNTR 3`UTR polymorphism of SLC6A3. Conclusion: Our findings do not support SLC6A3 as marker genetic susceptibility factor in adult ADHD. More comprehensive polymorphism coverage within the SLC6A3 region should be conducted in larger samples, including comparisons in clinical subgroups, and in samples with different ethnic backgrounds. (J. of Att. Dis. 2011; 15(4) 305-309)