Polymorphisms in genes involved in glucose metabolism in cases of sudden infant death syndrome.

Background: Infants with intra-uterine growth retardation have an increased risk of Sudden Infant Death Syndrome (SIDS). Hypoglycaemia is also significantly correlated with retardation of intra-uterine growth. A number of mutations in key proteins involved in regulation of blood glucose (e.g. glucokinase) have been found to result in reduced birth weight. Heterozygous mutations in the coding region of the glucokinase gene have been shown to cause MODY (a form of early onset Type II diabetes mellitus). The aim was to screen a cohort of SIDS and control infants who were either growth retarded or appropriately grown for gestational age to determine if any mutations and/or polymorphisms were present in the glucokinase gene.

Methods: PCR, denaturing high performance liquid chromatography on an automated Transgenomic WAVE DNA fragment analysis system and DNA sequencing.

Results: Genomic DNA was isolated from 129 infants who were either growth retarded or appropriately grown for gestational age. We found several rare novel polymorphisms in the glucokinase gene in the infant samples. However, none of the samples contained any of the mutations in the glucokinase gene previously reported in cases of MODY.

Conclusions: We have found rare novel polymorphisms in the glucokinase gene in the infant samples. In contrast in these samples, we have not found any examples of the previously reported mutations in the coding region of the glucokinase gene found in MODY. This clearly shows that while MODY babies are often small, MODY is not a common cause of either intra-uterine growth retardation or of SIDS.