FNDC5/Irisin polymorphisms are associated with osteopenia in postmenopausal Mayan-Mestizo women.

OBJECTIVE: This study aimed to analyze the association between rs3480 and rs16835198 of FNDC5/Irisin and their haplotypes with variations in bone mineral density (BMD) and osteopenia/osteoporosis in postmenopausal Mayan-Mestizo women. METHODS: We studied 547 postmenopausal women of Maya-Mestizo origin. BMD was measured in the lumbar spine and total hip by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time PCR allelic discrimination. Differences between the means of BMD according to genotype were analyzed with covariance. Allele frequency differences were assessed by χ2 and logistic regression was used to test for associations. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. RESULTS: Under a recessive model, we observed a significant association of rs3480 with the presence of osteopenia at the total hip and femoral neck (p = 0.008 and p = 0.003, respectively). For rs16835198, we found an association with osteopenia at the total hip and femoral neck in a dominant model (p = 0.043 and p = 0.009, respectively). CONCLUSIONS: We found an association of rs3480 with risk to present osteopenia at the total hip and femoral neck, while rs16835198 was associated as a protector for presence of osteopenia only at the femoral neck.

(-)-Epicatechin inhibits development of dilated cardiomyopathy in δ sarcoglycan null mouse.

BACKGROUND AND AIMS: Several studies propose that (-)-epicatechin, a flavonol present in high concentration in the cocoa, has cardioprotective effects. This study aimed to evaluate the impact of (-)-epicatechin on the development of dilated cardiomyopathy in a δ sarcoglycan null mouse model. METHODS AND RESULTS: δ Sarcoglycan null mice were treated for 15 days with (-)-epicatechin. Histological and morphometric analysis of the hearts treated mutant mice showed significant reduction of the vasoconstrictions in the coronary arteries as well as fewer areas with fibrosis and a reduction in the loss of the ventricular wall. On the contrary, it was observed a thickening of this region. By Western blot analysis, it was shown, and increment in the phosphorylation level of eNOS and PI3K/AKT/mTOR/p70S6K proteins in the heart of the (-)-epicatechin treated animals. On the other hand, we observed a significantly decreased level of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) heart failure markers. CONCLUSION: All the results indicate that (-)-epicatechin has the potential to prevent the development of dilated cardiomyopathy of genetic origin and encourages the use of this flavonol as a pharmacological therapy for dilated cardiomyopathy and heart failure diseases.

Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

Origin and genetic differentiation of three Native Mexican groups (Purépechas, Triquis and Mayas): contribution of CODIS-STRs to the history of human populations of Mesoamerica.

BACKGROUND: CODIS-STRs in Native Mexican groups have rarely been analysed for human identification and anthropological purposes. AIM: To analyse the genetic relationships and population structure among three Native Mexican groups from Mesoamerica. SUBJECTS AND METHODS: 531 unrelated Native individuals from Mexico were PCR-typed for 15 and 9 autosomal STRs (Identifiler™ and Profiler™ kits, respectively), including five population samples: Purépechas (Mountain, Valley and Lake), Triquis and Yucatec Mayas. Previously published STR data were included in the analyses. RESULTS: Allele frequencies and statistical parameters of forensic importance were estimated by population. The majority of Native groups were not differentiated pairwise, excepting Triquis and Purépechas, which was attributable to their relative geographic and cultural isolation. Although Mayas, Triquis and Purépechas-Mountain presented the highest number of private alleles, suggesting recurrent gene flow, the elevated differentiation of Triquis indicates a different origin of this gene flow. Interestingly, Huastecos and Mayas were not differentiated, which is in agreement with the archaeological hypothesis that Huastecos represent an ancestral Maya group. Interpopulation variability was greater in Natives than in Mestizos, both significant. CONCLUSION: Although results suggest that European admixture has increased the similarity between Native Mexican groups, the differentiation and inconsistent clustering by language or geography stresses the importance of serial founder effect and/or genetic drift in showing their present genetic relationships.

Expression analysis of the SG-SSPN complex in smooth muscle and endothelial cells of human umbilical cord vessels.

Recently, participation of the sarcoglycan (SG)-sarcospan (SSPN) complex in the development of cardiomyopathy in patients with limb-girdle muscular dystrophy has been shown, and presence of the complex in smooth muscle may be important for the contraction/dilation process of vessels. However, there are few studies determining the SG-SSPN complex in vascular smooth muscle and endothelial cells of vessels. In this study, we analyzed by reverse transcriptase-polymerase chain reaction and immunofluorescence the expression of different components of the complex in vein/artery smooth muscle and endothelial cells of the human umbilical cord. By RNA analysis, we observed expression of alpha-, beta-, gamma-, delta-, epsilon-SG, and SSPN in smooth muscle cells. In endothelial cells, RNA expression was restricted to beta-, delta-, epsilon-SG, and SSPN. At protein level, we observed in smooth muscle the presence of beta-, delta-, epsilon-SG, and SSPN. In endothelial cells, immunostaining only evidenced the presence of epsilon-SG and SSPN. However, colocalization of SGs and SSPN with dystrophin and utrophin was noted. These results, interestingly, suggest that the SG-SSPN complex may either form with dystrophin or utrophin in smooth muscle cells, and with utrophin in endothelial cells. Additionally, we also observed in some smooth muscle regions the colocalization of the SG-SSPN complex with caveolin, with colocalization being more pronounced between epsilon-SG-SSPN and caveolin in endothelial cells.