Dextromethorphan O-demethylation polymorphism in an African-American population.

OBJECTIVE: One hundred eighty-one (97 F, 84 M) unrelated healthy African-American subjects (aged 18-41 years) were phenotyped based on their dextromethorphan (DMP) O-demethylation ability. METHODS: Each subject was given 15 mg DMP orally and collected 8-h urine. The concentrations of DMP and its metabolite dextrophan (DOP) were determined by HPLC with ultraviolet detection. Metabolic ratio (MR) was expressed as the ratio of DMP to DOP molar amount in urine. RESULTS: The frequency distribution histogram of the MR was bimodal, and probit analysis of this frequency gave an antimode value of 0.34. Seven subjects [3.9%, 95% confidence interval (CI) 1.1%-6.7%] were classified as poor metabolizers (PMs). CONCLUSION: This deficient frequency is in complete agreement with the reported ones in two smaller investigations in the African-American populations.

Absence of linkage of the epithelial sodium channel to hypertension in black Caribbeans.

Hypertensives of African origin have low-renin, sodium-sensitive blood pressure and respond poorly to treatment with angiotensin converting enzyme inhibitors. The epithelial sodium channel may be important in the pathogenesis of essential hypertension in this population. This is supported by the identification of mutations within this channel, which lead to excess sodium reabsorption and hypertension in Liddle's syndrome. In this study we tested whether there was linkage of the genes encoding the three subunits of the epithelial sodium channel to essential hypertension in 63 affected sibling pairs of West African origin from St. Vincent and the Grenadines. We found no support for linkage of the epithelial sodium channel to essential hypertension in this population. However, further studies will be needed in larger populations of African ancestry to exclude a contribution of the genes encoding the epithelial sodium channel to hypertension.

The atrial natriuretic peptide gene and essential hypertension in African-Caribbeans from St Vincent and the Grenadines.

Atrial natriuretic peptide (ANP) which alters sodium balance, blood volume and vascular tone represents an important candidate for investigating the genetic basis of essential hypertension (EH). Accordingly, we have studied Bgl1 and Xho1 restriction fragment length polymorphisms (RFLPs) of the ANP gene in 147 hypertensive, 141 normotensive and 67 population-based control subjects from a homogenous population of West African origin from St Vincent and the Grenadines. We found no association of either Bgl1 and Xho1 RFLPs with EH. This study suggests that the ANP locus may not exert a major gene effect on EH amongst the black people of St Vincent and the Grenadines.

Genetic polymorphism of S-mephenytoin 4'-hydroxylation.

The anticonvulsant drug mephenytoin is available as a racemic mixture of the S and R enantiomers. The S enantiomer is selectively 4'-hydroxylated in the liver by the cytochrome P450 enzyme, CYP2C19. This reaction has a polymorphic distribution in human populations. Racemic mephenytoin has been extensively used as a probe drug to assign metabolic phenotypes for this genetically-determined polymorphism. Specific base substitution mutations in the CYP2C19 gene are responsible for the poor metabolism (PM) phenotype which is inherited as a recessive autosomal trait. The poor metabolizers (PMs) of S-mephenytoin are homozygous for these mutations. In contrast, extensive metabolizers (EMs) are either heterozygous or homozygous for the wild-type allele(s). Poor metabolizers have the inactive enzyme and therefore have reduced ability to metabolize substrates of CYP2C19, many of which are psychotropic drugs. Genotyping an individual before treatment with substrates of CYP2C19 will reduce the risk of side effects and improve compliance in PMs. The prevalence of PMs is relatively low in African-Americans and Caucasians and is as high as 20 percent in Asian populations.

Absence of genetic linkage between polymorphisms of the insulin receptor gene and essential hypertension.

This study evaluated whether hypertensive siblings had excess sharing of RsaI and SstI alleles of the insulin receptor gene compared with a random population. Thirty families consisting of 60 affected individuals with established hypertension were genotyped for the RsaI and SstI restriction fragment length polymorphisms and the resulting genotype data was analysed using the affected pedigree member method of linkage analysis. The hypertensive siblings were found to have increased sharing of INSR alleles; however, this linkage could not be confirmed using a maximum LOD score method. Thus, the results from this study do not support a role for the INSR gene in the genesis of essential hypertension in the population studied.

Efficacies of chloroquine, pyrimethamine/sulphadoxine and pyrimethamine/sulphalene against P. falciparum in northeastern Nigeria.

The clinical and parasitologic efficacies of oral chloroquine phosphate, pyrimethamine/sulphadoxine and pyrimethamine/sulphalene in treating Plasmodium falciparum malaria were assessed in selected sites of northeastern Nigeria (Zone D of the Primary Health Care (PHC) Programme) using a 14-day standard in-vivo protocol during 1988-1990. Of a total of 2056 children under 5 years screened for infection, for chloroquine trials, 1189 (57.8%) were positive for Plasmodium infection. One hundred and seventy (14.3%) of these positive children were enrolled into the study. Clinically, the drug demonstrated high performance in clearing symptoms of infection. However, varying degrees of parasitologic failure, ranging from delayed clearance through recrudescence to asymptomatic Type-II resistance, were encountered. For tests with pyrimethamine/sulphadoxine and pyrimethamine/sulphalene, 517 and 253 children, respectively, were screened. The corresponding infection rates were 71.6% (370 children) and 71.5% (181 children), with 59 and 34 enrollments. Both drugs were highly effective, clinically and parasitologically. These findings and their implications for the success of the PHC programme for malaria control are discussed.

Efficacy of chloroquine in the treatment of malaria in children under five years in Baissa (Gongola State, Nigeria).

The Nigerian Federal Ministry of Health in 1987 instituted a nationwide programme to gather data on the efficacy of chloroquine in treating malaria in children as a basis for the development of a national malaria therapy policy. The programme is part of a comprehensive Combating Childhood Communicable Diseases (CCCD) programme. A simplified WHO in vivo method, involving follow-up observations on day 1 (D1), D2, D7 and D14 following the first day the study began (D0), was used for this study. A total of 769 children were screened, of which 363 (47%) were positive for malaria parasites. Fifty-three children were enrolled for the 14-day follow up, and chloroquine phosphate, 25 mg (base) kg-1, was given in three divided doses on D0, D1 and D2. Parasitological failure occurred in 25% of the children. There were no clinical failures in the study; i.e. no child found with parasitaemia after completing treatment was judged to be clinically ill. Generally the older children had the heavier parasite densities and severer symptoms.