Abstract
BackgroundThere are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and −460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy.MethodsIn the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF −460 polymorphisms using a pyrosequencing technique.ResultsForty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF −460 genotypes. The distributions of the VEGF +405 and VEGF −460 genotypes were similar between the diabetic patients with and without neuropathy.ConclusionsIn this cohort of patients, VEGF +405 and VEGF −460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds.
Highlights
There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy
We found that the distribution of the genetic polymorphisms of vascular endothelial growth factor (VEGF) +405 and VEGF-460 varied with ethnic origin, but differences were not found to be associated with the presence of peripheral neuropathy in this cohort of patients with diabetes
The present study is the first to examine the distribution of VEGF +405 and VEGF −460 genotypes in AfricanCaribbean, Indo-Asian and Caucasian patients with diabetes and the association of these genotypes with peripheral neuropathy
Summary
There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. Population based studies in the United Kingdom (UK) have reported lower rates of peripheral neuropathy in patients with type 2 diabetes of Indo-Asian and African-Caribbean origin compared with those of Caucasian origin [7,8,9]. Studies showing evidence of increased skin microvascularization in Indo-Asian subjects has been considered a cause for the lower rates of neuropathy compared with Caucasian subjects [10]. These findings were independent of glycaemic control and traditional risk factors for vascular disease, suggesting that genetic, or some other, as yet unidentified protective factor(s) may be relevant to these observations
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