Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1alpha in Africans with diabetes.
BACKGROUND
Clinical presentation and natural history of diabetes are somewhat different in Black Africans compared to Caucasians. This peculiar disease course could be at least partly related to a specific genetic profile that has not been studied in this population.


METHODS
Medical backgrounds, anthropometric and biologic parameters were obtained from 69 diabetic subjects in Dakar, Senegal, in 1998. Blood anti GAD and Islet Cell Antibodies were studied, using RIA and immunofluorescence assay. The HNF-1alpha gene was sequenced searching the Gly574Ser mutation, previously described in MODY 3.


RESULTS
Among these 69 diabetic patients, 11 (16%) were found to have the G574S mutation affecting the HNF-1alpha. These 11 patients carrying the mutation were compared respectively with the 58 non carriers. Mean age (57.5 yr. +/- 11 vs 51.1 yr. +/- 15) and duration of diabetes (11.9 vs 6.7 yr), were similar in the two groups. BMI was not different in patients with the mutation (26.3 vs 23.3, p=0.06). Metabolic control (Glycosylated hemoglobin) was poor in the two groups (9.5% vs 9.2%). Chronic complications were equally found in the patients, but no mutation carrier had macroangiopathy. None of the anti GAD positive or ICA positive patients had the mutation.


CONCLUSIONS
The HNF-1alpha Gly574Ser mutation was found in 16% of cases in a 69 diabetic patients group in Senegal. Diabetes was as severe as in non carriers of mutation. This mutation has been implicated in atypical diabetes of Afro-American children. The study confirms its prevalence in Africans with diabetes.
Collet
C
C
Service d'Endocrinologie, Hôpital d'Instruction des Armées Bégin, 94160 Saint Mandé, France.
Ducorps
M
M
Mayaudon
H
H
Dupuy
O
O
Ceppa
F
F
Boutin
P
P
Froguel
P
P
Bauduceau
B
B
D000328:Adult; D000349:Africa / Q000208:ethnology; D019943:Amino Acid Substitution; D044383:Black People / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005602:France; D006580:Genetic Carrier Screening; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009687:Nuclear Proteins; D010641:Phenotype; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta