Acetylation pharmacogenetics and renal function in diabetes mellitus patients.

Activities of human hepatic drug metabolizing enzymes N-acetyl transferase (NATS) had earlier been recognized as a cause of inter-individual variation in the metabolism of drugs. Therefore acetylation of many drugs in human exhibit genetic polymorphism. The aim of the study was to investigate if acetylator status predispose diabetic mellitus patients more to the complications of renal disease, One hundred and twenty (120) diabetics consisting of (50) Type 1 (T(1)) and 70 Type 2 (T(2)) diabetes mellitus patients and 100 healthy individuals as controls were classified as slow or rapid acetylator using sulphamethazine (SMZ) as an in vivo probe. The percentage acetylation, recovery of SMZ, creatinine clearance and presence of urinary albumin were determined. A significant difference (P < 0.05) was observed in the percentage of SMZ acetylated between slow and rapid acetylators in control, T(1) and T(2) subjects. The ratios of slow to rapid acetylators for T(1), T(2) and control subjects were 1:4, 3:2 and 2:3 respectively. No significant differences were observed in the percentage of SMZ recovered in the urine of slow and rapid acetylators that are diabetics. The difference in creatinine clearance of slow and rapid acetylators in T(1) and T(2) were significant (P < 0.05). 29% out of 120 (24.2%) diabetics (T(1) and T(2)) exhibited albuminuria out of which 25 (86.2%) had slow acetylator status. These findings suggest that slow acetylator status in diabetes mellitus could be a predisposing factor in the development of renal complications. This underscores the need for a rapid pharmacogenetic testing and therapeutic drug monitoring in such patients. However this inference could be further validated with a larger sample size.

Carboxyhaemoglobin levels in some Lagos dwellers--a pilot study.

Carboxyhaemoglobin (COHb) concentrations were determined by differential spectrophotometry in blood of 60 healthy adult subjects from various locations in Lagos. Half of these were either occasional or regular tobacco cigarette smokers. Our findings showed that the Lagos dweller has elevated COHb concentration ranging between 7.6%-9.9%, several folds higher than permitted by Air Quality Standards. The range and scatter of COHb in smokers were wider (7.4%-13.0%) than in non smokers. In particular, COHb concentrations were significantly higher in regular smokers than in non smokers by Fisher's exact test (p < 0.0006). Elevated COHb concentrations among smokers were related to frequency of tobacco use (p < 0.01). There was however no statistically significant difference in COHb concentrations when the regular and occasional smokers were taken as a group and compared with the non smokers. Haematocrit measurements showed that a degree of anaemia was present in most of the subjects tested irrespective of smoking status (mean packed cell volume = 36.1). It is inferred from this data that the Lagos dweller has high ambient concentrations of COHb and that these may be further aggravated by cigarette smoking.

HLA class I phenotype and gene frequencies in parts of southern Nigeria.

HLA-A, B and C antigens were determined in 101 healthy subjects from two major and several minor ethnic groups in some parts of Southern Nigeria. Compared to earlier data based on a panel of expatriate Nigerians, significant differences were observed in antigen phenotype and gene frequencies particularly at the HLA-A locus. At least three antigenic specificities not previously observed in the expatriate Nigerians were detected in the present study. These included HLA-B8. B14 and CW1. These antigens however occurred at low frequencies. The antigens A23 and B7 were in positive linkage disequilibrium along with others which involved CW4 with B53 or B35. It is concluded from our findings that HLA polymorphisms in Nigerians may not be completely reflected in major population group studies alone. It is possible that more specificities may be detected by continued testing of the minor ethnic groups. The importance of this could be immense in disease association studies involving HLA genes as well as in anthropology.