Mecanismos fisiopatológicos de la sarcopenia en la EPOC / Pathophysiological mechanism of sarcopenia in COPD

La sarcopenia es una enfermedad caracterizada por la pérdida de masa muscular, fuerza muscular y rendimiento físico, siendo la principal causa de fragilidad en los adultos mayores. La sarcopenia es altamente prevalente en individuos con enfermedad pulmonar obstructiva crónica (EPOC) que conduce a un mal pronóstico y una mayor mortalidad en esta población. La presencia de sarcopenia en la EPOC es probablemente el resultado de la interacción entre factores externos e internos como la inflamación sistémica, el estrés oxidativo y los polimorfismos genéticos, frecuentemente observados en individuos con esta enfermedad respiratoria. Esta revisión resume el conocimiento sobre los mecanismos patogénicos asociados con la sarcopenia en la EPOC.

Sarcopenia is a disease characterized by loss of skeletal muscle, muscle strength and physical performance, being the major cause of frailty in the elderly. The sarcopenia is highly prevalent in individuals with Chronic obstructive pulmonary disease (COPD) leading to a poor prognosis and higher mortality in this population. The presence of sarcopenia in COPD is likely the result by the interaction between external and internal factors as systemic inflammation, oxidative stress and genetic polymorphisms, frequently observed in individuals with this respiratory disease. This review summarizes the current knowledge about the pathogenic mechanisms linking COPD with sarcopenia.

Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion / Metabolismo e polimorfismos gênicos da via do folato em mulheres brasileiras com história de aborto recorrente

PURPOSE: To investigate the association between polymorphisms in genes that encode enzymes involved in folate- and vitamin B12-dependent homocysteine metabolism and recurrent spontaneous abortion (RSA). METHODS: We investigated the C677T and A1298C polymorphisms of the methylenetetrahydrofalate reductase gene (MTHFR), the A2756G polymorphism of the methionine synthase gene (MS) and the 844ins68 insertion of the cystathionine beta synthetase gene (CBS). The PCR technique followed by RFLP was used to assess the polymorphisms; the serum levels of homocysteine, vitamin B12 and folate were investigated by chemiluminescence. The EPI Info Software version 6.04 was used for statistical analysis. Parametric variables were compared by Student's t-test and nonparametric variables by the Wilcoxon rank sum test. RESULTS: The frequencies of gene polymorphisms in 89 women with a history of idiopathic recurrent miscarriage and 150 controls were 19.1 and 19.6% for the C677T, insertion, 20.8 and 26% for the A1298C insertion, 14.2 and 21.9% for the A2756G insertion, and 16.4 and 18% for the 844ins68 insertion, respectively. There were no significant differences between case and control groups in any of the gene polymorphisms investigated. However, the frequency of the 844ins68 insertion in the CBS gene was higher among women with a history of loss during the third trimester of pregnancy (p=0.003). Serum homocysteine, vitamin B12 and folate levels id not differ between the polymorphisms studied in the case and control groups. However, linear regression analysis showed a dependence of serum folate levels on the maintenance of tHcy levels. CONCLUSION: The investigated gene polymorphisms and serum homocysteine, vitamin B12 and folate levels were not associated with idiopathic recurrent miscarriage in the present study. Further investigations are needed in order to confirm the role of the CBS 844ins68 insertion in recurrent miscarriage. .

OBJETIVO: Investigar a associação entre polimorfismos nos genes que codificam enzimas envolvidas no metabolismo da homocisteína dependente de folato e vitamina B12 e aborto espontâneo recorrente. MÉTODOS: Investigamos os polimorfismos C677T e A1298C no gene methilenotetrahidrofalato redutase (MTHFR); o polimorfismo A2756G no gene metionina sintase (MS) e a inserção 844ins68 no gene da cistationina beta-sintetase (CBS). A técnica de PCR seguido por RFLP foi utilizada para investigar os polimorfismos. Os níveis séricos de homocisteína, vitamina B12 e de folato foram investigados pela técnica de quimioluminescência. O Software Epi Info versão 6.04 foi utilizado para realizar a análise estatística. As variáveis paramétricas foram comparadas pelo teste t de Student e as variáveis não paramétricas pelo teste de Wilcoxon rank sum. RESULTADOS: As frequências dos polimorfismos gênicos em 89 mulheres com história de aborto recorrente idiopático e 150 controles foram de 19,1 e 19,6% para o C677T; 20,8 e 26% para o A1298C; 14,2 e 21,9% para o A2756G e 16,4 e 18% para a inserção 844ins68, respectivamente. Não houve diferenças significantes entre os grupos caso e controle em todos os polimorfismos dos genes investigados. No entanto, a frequência da inserção 844ins68 no gene CBS foi maior entre mulher com histórico de perdas no terceiro trimestre da gravidez p=0.003). Os níveis de homocisteína, vitamina B12 e folato séricos não foram diferentes entre os polimorfismos estudados nos grupos casos e controles. No entanto, a análise de regressão linear mostrou dependência dos níveis séricos de folato na manutenção dos níveis de homocisteína. CONCLUSÃO: Os polimorfismos gênicos investigados, assim como homocisteína, vitamina B12 e os níveis séricos de folato não foram associados com abortos recorrentes idiopático no presente estudo. Novas investigações devem ser realizados a fim de confirmar o papel da inserção 844ins68-CBS nos abortos recorrentes. .

Polymorphisms of complement genes and ARMS2/HTRAI in patients with age-related macular degeneration in Ningxia, China / 中华实验眼科杂志

Background Age-related macular degeneration (AMD) is the main cause of irreversible loss of central vision in old population.The incidence of AMD is increasing year by year,but the mechanism is not clearly understood.Objective This study was to investigate the association between genetic variants and the risk of AMD in Ningxia population.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and complied with the Helsinki Declaration.Written informed consent was obtained from each subject.One hundred and fifty patients with AMD and 145 ethnicity-and gender-matched controls were recruited in Ningxia Eye Hospital from January 2012 to March 2013.All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood.The single nucleotide polymorphisms (SNPs) of 8 susceptibility loci in four candidate genes,including complement factor H (CFH),complement factor B (CFB),age-related maculopathy susceptibility 2 (ARMS2) and high temperature required factor A1 (HTRA1),were genotyped with Mass Array and MALDI-TOF technique by Sequenom platform.The distribution of genotype was tested for Hardy-Weinberge equilibrium (HWE).The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls using chi-squared test and the P value was significant at ＜ 0.006 level after correction of age,and the relationship of genotype distribution with AMD was evaluated by Logistic regression analysis.Measures of linkage disequilibrium (LD) was carried out by Haploview.Results All the genetypes met HWE.Seven SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls (all at P＜ 0.05),however,after Bonferroni correction,the differences of only four SNPs were significant between the patients and controls in the genotype and allele distributions,including the SNPs of rs10737680 and rs1410996 in CFH gene,the SNP of rs10490924 in ARMS2 gene and SNP of rs11200638 in HTRA1 gene.The allele distributions of rs800292 (Pallele =0.006,OR =1.643,95 ％ CI:1.155-2.336) in CFH and rs641153 (Pallele =0.002,OR =0.273,95 ％ CI:0.120-0.620) in CFB were significantly associated with AMD.In addition,five SNPs in CFH gene were consisted of two blocks after analysis by Haploview.In addition,five SNPs in CFH were consisted of two blocks after analysis by Haploview.The first one SNPs (including rs551397 and rs800292) and another one SNPs (including rs12124794,rs10737680) and rs1410996 were in strong linkage disequilibrium (D'=1.00).After 50 000 permutations,the GC and AT haplotypes of the first block and the AAC,TCT and ACT haplotypes in the second block were significantly different between AMD patients and controls (P =0.010,0.010,0.001,0.041 and 0.033,respectively).The allel T of rs641153 was a protective factor of AMD (P=0.002,OR =0.273,95％ CI:0.120-0.620).Conclusions The SNPs rs10737680 and rs1410996 in CFH,rs10490924 of ARMS2 gene and rs11200638 of HTRA1 gene are associated with AMD in Ningxia population.

Relationship between 5-hydroxytryptamine 1A receptor and G-protein β3 subunit polymorphisms and post-stroke depression / 中华神经科杂志

Objective To assess whether 5-HTR1A C( - 1019) G and GNβ3 C825T gene polymorphisms are associated with post-stroke depression (PSD) and explore the genetic mechanism of the pathogenesis of post-stroke depression. Methods All 159 patients with first stroke were divided into the PSD group and the control group according to HAMD scores. Their genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Results The frequency of 5-HTR1A (-1019) GG genotype(8/53,15. 1% ), G allele (44/106,41.5%)and GNβ3 825T allele(68/106,64. 2% ) were significantly higher in the post-stroke depression group than in the controls (5/106,4.7% ;35/212, 16. 5%; 113/212, 53.3%; ×2 = 23.204, 23. 655, 3. 392, all P ＜ 0. 05 ). Combined genotype analysis showed that individuals with both 5-HTR1A ( - 1019) G and GNβ3 825T allele ( OR =4. 980,95% CI 2. 429-10. 210,P =0. 000) had a higher risk than those with 5-HTR1 A (-1019) G allele ( OR = 3. 589,95% CI 2. 113-6. 096, P = 0. 000) or GNβ3 825T allele ( OR = 0. 638,95% CI 0.395-1. 031 ,P =0. 042) only for post-stroke depression. Conclusion The 5-HTR1A C( - 1019)G and GNβ3 C825T polymorphisms are predisposing genes of post-stroke depression. Our data also suggest a significant interaction between the 5-HTR1A ( - 1019)G allele and GNβ3 825T allele in post-stroke depression.

Relationship between CX3CR1 polymorphisms and carotid artery stenosis / 中华神经科杂志

Objective To study the association of V249I and T280M polymorphisms of fractalkine receptor CX3CR1 with carotid artery stenosis (CAS). Methods 318 patients with CAS diagnosed using color Doppler ultrasound criteria were studied and compared with 292 subjects without CAS. V249I and T280M polymorphic genotypes of CX3CR1 were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing analysis. Results The genotypes of MM and TM were associated with reduced risk of CAS,the frequency of genotype MM + TM in the two groups being 22. 6% and 31.2% respectively ( OR = 0. 646, 95% CI 0. 451-0. 928, P = 0. 017), the frequency of M allele was significantly lower in patients with CAS than in those without CAS ( 13.8% and 19. 2% respectively, OR = 0. 677, 95%CI 0.499--0. 918,P=0. 010). No differences were observed in the Ⅱ, Ⅵ, or VV genotype, the frequency of genotype Ⅱ + Ⅵ in the two groups being 39. 0% and 43.8% respectively ( OR = 1. 012, 95% CI 0. 731-1. 403 ,P = 0. 940), the frequency of Ⅰ allele was significantly lower in patients with CAS than in those without CAS (28. 6% and 32. 7% respectively, OR = 0. 842, 95% CI 0. 660-1. 076, P = 0. 034). The genotypes of Ⅱ and Ⅵ in patients with stable plaques were more frequent than in vulnerable plaques( OR = 0. 610, 95% CI 0. 387-0. 962, P = 0. 033 ). Multiple Logistic regression analysis revealed that the genotypes of MM and TM were an independent risk factor for CAS ( OR = 1. 847,95% CI 1. 091- 3. 127 ,P = 0. 022). Conclusion The genotypes of MM and TM are independent risk factors for carotid artery stenosis, and the genotypes of Ⅱ and Ⅵ are associated with the stability of carotid artery plaques.