ABSTRACT
A cooperative role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and superoxide dismutase 2 (SOD2) to maintain the vascular function has recently been demonstrated in nitrate tolerance. The present study examined whether the combination of low enzyme-activity variants of ALDH2 and SOD2 increases the risk of hypertension in relation to alcohol consumption. A total of 444 Japanese participants in a health-screening program were evaluated. The risk of hypertension among the individuals harboring both the ALDH2*2 allele and the SOD2 Val/Val genotype was significantly higher in drinkers than in nondrinkers (adjusted odds ratio, 6.22; 95% confidence interval, 2.26-17.1; P<0.001). Among these individuals, the systolic/diastolic blood pressure also increased by 0.24/0.14 mmHg for each 1g/day increase in alcohol consumption (P<0.001/P=0.003). These associations were observed, but the degree was lower among those with the other genotype combinations (0.11/0.10 mmHg; P=0.012/P=0.001). Information about the genetic predisposition to alcohol-related diseases may thus be useful to promote lifestyle modifications for high-risk individuals.
Subject(s)
Alcohol Drinking/adverse effects , Aldehyde Dehydrogenase/genetics , Hypertension/etiology , Mitochondria/enzymology , Polymorphism, Genetic/genetics , Superoxide Dismutase/genetics , Aldehyde Dehydrogenase, Mitochondrial , Alleles , Asian People/genetics , DNA/genetics , Female , Genotype , Humans , Hypertension/enzymology , Male , Middle Aged , Polymerase Chain Reaction , Risk FactorsABSTRACT
Antisense technology provides an effective strategy to inhibit synthesis of the gene product. We prepared a novel antisense reagent comprised of oligodeoxynucleotides (ODN) and a thermo responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm). The conjugate inhibited gene expression in a dose-dependent manner. The ODN-PNIPAAm conjugate demonstrated excellent resistance to S1 nuclease. In particular, PNIPAAm-modified antisense ODN at the 3',5'-ends of the ODN provided complete resistance against nuclease at 37 degrees C, which is above the phase transition temperature of the PNIPAAm side chain. These characteristics of the conjugate suggest it may have potential for use in a new gene delivery system as part of an antisense strategy.
Subject(s)
DNA/chemistry , Deoxyribonucleases/metabolism , Oligodeoxyribonucleotides, Antisense/chemical synthesis , Oligodeoxyribonucleotides, Antisense/pharmacology , Base Sequence , DNA/drug effects , Deoxyribonucleases/antagonists & inhibitors , Drug Design , Gene Expression Regulation/drug effects , Indicators and Reagents , Kinetics , Oligodeoxyribonucleotides/chemical synthesis , Oligodeoxyribonucleotides/pharmacologyABSTRACT
3'-methacryloyl-oligodeoxynucleotide having antisense sequence against messenger RNA of green fluorescent protein and N-isopropylacrylamide were co-polymerized. The conjugate can reversibly change its conformation at around a transition temperature, similarly to N-isopropylacrylamide homopolymer. We achieved artificially regulation of gene expression depending on temperature using the conjugate.
