The polymorphism Arg585Gln in the gene of the sterol regulatory element binding protein-1 (SREBP-1) is not a determinant of ketosis prone type 2 diabetes (KPD) in Africans

Aim. - Ketosis prone type 2 diabetes (KPD) is an atypical form of diabetes described mainly in People of sub-Sabaran African origin. Its pathogenesis is unknown, although we have previously described a high prevalence of glucose-6-phosphate-dehydrogenase (G6PD) deficiency in patients with KPD. However, 50% of these deficient patients lacked the G6PD gene mutation. The isoforms of the transcription factor sterol regulatory element binding protein 1 (SREBP-1) are known to stimulate GOPD gene expression, and some polymorphisms in the SREBP-1 gene (SREBF-1) have been described only in Africans. We investigated one of these, the Arg585Gln polymorphism, in a candidate gene approach for KPD. Methods. - We examined the presence of the Arg585Gln polymorphism in SREBF-1 in 217 consecutive unrelated Africans 173 patients with KPD. 80 with classical type 2 diabetes (T2D) and 64 nondiabetic Subjects]. Patients underwent clinical and biochemical evaluations, and were assessed for G6PD activity and insulin secretion (glucagon test). Results. - There were no differences in frequency of the Arg585Gln polymorphism and the 585Gln allele among the three groups (allele frequency: KPD: 0.089. T2D: 0.031. nondiabetic group: 0.070; P=0.1). When the 585Gln allele frequency was compared separately between patients with KPD and those with T2D, it was significantly higher in the former (P=0.032). There was no difference between carriers and noncarriers of the 595Gln allele regarding, G6PD activity and insulin secretion. Conclusion. - The results of this exploratory study show that the polymorphism Arg585Gln in SREBF-1 is not associated with the KPD phenotype. Further Studies in larger populations are needed to confirm our findings. (C) 2008 Elsevier Masson SAS. All rights reserved.