[Associations of genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with low birth weight in neonates].

OBJECTIVE: To investigate whether genetic polymorphisms in the microsomal epoxide hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are associated with low birth weight in neonates. METHODS: Using standard questionnaires, 246 singleton live born mother-neonates pairs (73 cases were mother-low birth weight neonate pairs and 173 controls were mother-non low birth weight neonate pairs) were investigated by the trained field workers with case-control study at the hospital in Anqing, Anhui Province, China between 1998 and 1999. A total of 246 neonates were genotyped for genetic polymorphisms in the EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Multiple linear regression models were used to estimate the association of the genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education, parity, neonatal sex and gestational age. RESULTS: EPHX1 His139His homozygote was not associated with low birth weight among neonates, compared with EPHX1 His139Arg heterozygote/Arg139Arg homozygote before and after adjustment confounders. GSTT1 absent genotype group also was not associated with low birth weight among neonates, compared with GSTT1 present genotype group before and after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1 polymorphism were considered, a significant reduction in birth weight was found among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype (OR=3.46, P=0.035). CONCLUSION: The combination between genetic polymorphisms in the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with neonatal low birth weight.

[The application of RNAi to the medical genetics].

Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messenger RNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation. Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.

Mother's and child's methylenetetrahydrofolate reductase C677T polymorphism is associated with preterm delivery and low birth weight.

OBJECTIVE: To investigate the association of the C677T polymorphism of the 5,10-methyleneterahydrofolate reductase(MTHFR) gene with preterm delivery(PTD) and low birth weight (LBW). METHODS: A total of 250 normal gestational age families and 250 PTD families were enrolled in the study. Polymerase Chain Reaction (PCR) followed by restriction enzyme digestion were used for genotyping the polymorphism of MTHFR C677T. A Maximum Likelihood Ratio Test approach based on the log-linear model was used to analyze the relationship of MTHFR gene polymorphism and risk of PTD and LBW. RESULTS: Firstly, we checked the Mendelian transmissions of the variant alleles of MTHFR 677T in PTD and LBW control-parent-triads using TDT test, respectively. These analyses of controls support Mendelian transmission. When children's genotypes were considered, the MTHFR CT and TT genotypes could significantly increase the risk of PTD and LBW, compared to the genotype of MTHFR CC, the odds ratio and 95% confidence interval (CI) for MTHFR CT and TT genotypes were 2.01,1.21-3.32 1.82, 1.02-3.26 in PTD group, and were 1.87, 1.08-3.24;1.90, 1.02-3.54 in LBW group respectively. When mother's genotypes were considered, the MTHFR gene polymorphism was not associated with PTD and LBW. Meanwhile, we also examined the association of mothers' and children's combined genotypes of MTHFR C677T with the risk of PTD and LBW, and did not find any significant interaction between mothers' and children's genotypes. CONCLUSION: The infant MTHFR CT and TT genotypes are responsible for mothers' PTD and LBW in our study population. It supports that the non-Mendelian transmission among preterm children is due to a causal association between the MTHFR 677T variant alleles and preterm delivery and MTHFR gene likely affects LBW via shortened gestation (PTD).

[Associations of Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism in neonates with preterm delivery].

The objective is to investigate whether Rsa I polymorphism at the 5' flanking region of cytochrome P450 2E1 gene (CYP2E1) and paraoxonase 2 gene polymorphism (PON2 148) in neonates are associated with preterm delivery. Using standard questionnaires, 209 singleton live born mother-neonate pairs (include preterm cases and term controls) were investigated by the trained field workers with cross-sectional survey at the hospitals in Anqing, Anhui Province, China. Epidemiological and clinical data and blood samples were obtained from 209 mother-neonate pairs. CYP2E1 homozygous wild-type (+/+) is not associated with a shortened gestation among neonates, compared with CYP2E1 homozygous mutant-type (-/-)/CYP2E1 heterozygote (+/-) before and after adjustment confounders, however, PON2 Ala148Ala homozygote is significantly associated with a shortened gestation among neonates. When Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism were considered jointly, a significant shortened gestation was observed among neonates with the combined genotype of CYP2E1 homozygous wild-type and PON2 Ala148Ala homozygote. In conclusion, Rsa I polymorphism at the 5' flanking region of CYP2E1 in neonates is not associated with preterm delivery, however, PON2 148 polymorphism in neonates is significantly associated with preterm delivery. Furthermore, the gene interaction between Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism in neonates is significantly associated with preterm delivery.

[Effect of wolfberry fruit and epimedium on DNA synthesis of the aging-youth 2BS fusion cells].

OBJECTIVE: To study the effect of water extracts of Wolfberry fruit (WB) and Epimedium (EM) on DNA synthesis of the aging-youth 2BS fusion cells. METHODS: Human embryonic lung diploid fibroblasts 2BS national standard strain, were used as an aging model. Cell denucleation and cell fusion techniques were applied to observe the effect of WB and EM on DNA synthesis of 2BS fusion cells. RESULTS: In the 0.025 (V/V) WB or EM water extract containing media, 2BS cells could be continuously cultured for 61.0 +/- 2.9 passages and 56.0 +/- 2.6 passages respectively, while in the control group it was only 49.0 +/- 2.6 passages (P < 0.01). After treatment with WB and EM separately for 2 hrs, the aging 2BS cells were denucleated and fused with young 2BS cells. The [3H]TdR incorporation percentage in these treated cells was significantly higher than that in the untreated control cells (P < 0.01). CONCLUSION: Both WB and EM can accelerate the DNA synthesis rate of the aging youth 2BS fusion cells and prolong the life span of 2BS cells.

[Association of CYP2E1 of PON2311 polymorphisms in neonates with preterm].

The objective is to investigate whether Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates are associated with preterm. Using standard questionnaires, 194 singleton live born mother-neonate pairs (including preterm cases and term controls) were investigated by the trained field workers with cross-sectional survey at the hospitals in Anqing, Anhui Province, China. Epidemiological and clinical data and blood samples were obtained from 194 mother-neonate pairs. CYP2E1 homozygous wild-type (cut/cut) is not associated with a shortened gestation among neonates, compared with CYP2E1 homozygous mutant-type (uncut/uncut)/CYP2E1 heterozygote (cut/uncut) before and after adjustment confounders. However, PON2 Ser311Ser homozygote is significantly associated with a shortened gestation among neonates. When Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism were considered jointly, a significant shortened gestation was observed among neonates with the combined genotype of CYP2E1 homozygous wild-type and PON2 Ser311Ser homozygote. In conclusion, Rsa I polymorphism in the 5'-flanking region of CYP2E1 in neonates is not associated with preterm, however, PON2311 polymorphism in neonates is significantly associated with preterm. Furthermore, the gene interaction between Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates is significantly associated with preterm.