[Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum].

OBJECTIVE: To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy. METHODS: Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot. RESULTS: The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF-α mRNA expression than the 10% septic serum group (P<0.01), but IL-1ß mRNA expression showed no significant difference between the two groups. CONCLUSIONS: UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.

Functional variant in methionine synthase reductase decreases the risk of Down syndrome in China.

AIM: Down syndrome (DS) is the most common genetic cause of human mental retardation and the genes involved in homocysteine/folate metabolism may play important roles in this condition. Methionine synthase reductase (MTRR) is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine. We investigated whether the polymorphism C524T of the MTRR gene is associated with DS. METHOD: A total of 104 mothers of children born with DS and 184 healthy mothers were included. The polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism analysis. Plasma folate and total plasma homocysteine (t-Hcy) concentrations were also measured. RESULTS: Significant differences in the distributions of C524T alleles were observed between case and control mothers; a decreased risk of DS was associated with the 524TT genotype (OR=0.34), CT+TT genotype (OR=0.60). The mean t-Hcy value in the case group was higher than the mean value in the control group. t-Hcy concentrations were lower in TT homozygote than CC homozygote among the cases but not among the controls. CONCLUSION: MTRR C524T polymorphism decreases the risk of DS in the Chinese population.

Polymorphisms in genes RFC-1/CBS as maternal risk factors for Down syndrome in China.

PURPOSE: To explore the relationship between genetic polymorphisms in reduced folate carrier 1 (RFC-1), cystathionine b-synthase (CBS), two key genes in folate metabolism, and the risk of Down syndrome in China. METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 104 mothers born children with Down syndrome and 184 age-matched control mothers. Polymerase chain reaction and restriction-fragment length polymorphism were used to examine the polymorphisms of RFC-1 A80G, CBS T833C and the relationship between these genotypes and the risk of Down syndrome was analyzed. RESULTS: We found that there were significant differences between RFC-1 G80G, CBS C833C polymorphisms among mothers of children with Down syndrome than among control mothers, with odds ratio of 1.51 (95 % CI 1.05-2.18), 1.53 (95 % CI 1.07-2.18) respectively. The combined presence of RFC1 mutant alleles and the CBS homozygous mutant allele (15/104) was associated with a 4.81-fold increased risk of having a child with Down syndrome (95 % CI 1.82-12.68, P = 0.0007). CONCLUSIONS: We concluded that RFC-1 and CBS gene mutation alleles are related to Down syndrome, and women with mutation RFC-1 G80G, CBS C833C OR combined with RFC-1 A80G and CBS 833TT genotype increase the risk of Down syndrome in China.

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China.

OBJECTIVE: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C-->T, MTRR 66A-->G and the relationship between these genotypes and the risk of Down syndrome was analyzed. RESULTS: The results show that the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78 approximately 8.47). In addition, the homozygous MTRR 66A-->G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90 approximately 14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058 approximately 17.496). The two polymorphisms appear to act without a multiplicative interaction. CONCLUSION: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.