[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.

[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.

[Association of PON2 gene polymorphisms in neonates with preterm].

Branch of Institute for Biomedicine,Anhui Medical University,Anqing 246000,China Abstract:The objective is to investigate whether gene polymorphisms in the PON2 gene (PON2148 and PON2311) of neonates are associated with preterm. Using standard questionnaires,194 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 194 mother-neonate pairs. Among neonates,PON2 Ala148Ala homozygote is significantly associated with preterm,compared with Gly148Gly homozygote / Ala148Gly heterozygote before and after adjustment confounders and the same was true for PON2 Ser311Ser homozygote. However,when PON2148 polymorphism and PON2311 polymorphism were considered jointly,no significant gene interaction between PON2148 polymorphism and PON2311 polymorphism in relation to preterm was observed. We draw a conclusion from this research that both PON2148 polymorphism and PON2311 polymorphism in neonates are significantly associated with preterm respectively. But the gene interactions between PON2148 polymorphism and PON2311 polymorphism in neonates are not significantly associated with preterm.

[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.