Association of the polymorphisms 292C>T and 1304G>A in the SLC38A4 gene with hyperglycaemia

Background The SLC38A4 gene is related to system 'A' activity, which seems to be related to impaired gluconeogenesis. The objective of this study was to determine whether the 292C>T and 1304G>A polymorphisms of SLC38A4 gene are associated with hyperglycaemia in humans. Methods A total of 227 individuals were enrolled in a case-control study, in which hyperglycaemia was defined by plasma glucose levels ≥95mg/dL. Genotyping was carried out by using real-time polymerase chain reaction. Results The frequency of mutant alleles of SLC38A4 gene for single-nucleotide polymorphism (SNP) 1304G>A was 23.6% and 30.2% for SNP 292C>T. The frequency of allele T for the SNP 292C>T in the case and control groups did not show significant differences, whereas the frequency of allele A for the SNP 1304G>A was significantly higher in the case group than in the control group (p=0.04). In the logistic regression analysis, the SNP 1304G>A [odds ratio (OR) 1.78; 95%CI 1.04-3.05, p=0.03] but not SNP 292C>T (OR 1.41; 95%CI 0.80-2.47, p=0.23) showed a significant association with hyperglycaemia. After adjusting by body mass index, waist circumference and triglycerides, the SNP 1304G>A remained significantly associated with hyperglycaemia (OR 2.13; 95%CI 1.18-3.83, p=0.03). Pair wise linkage disequilibrium showed correlation (D'>0.82) between 292C>T and 1304G>A SNPs. Haplotype association with hyperglycaemia also showed significant association between both homozygous mutant alleles (A/T) and hyperglycaemia (OR 1.68; 95%CI 1.01-2.79, p=0.048). Conclusions Our results suggest that mutant allele A for SNP 1304G>A of SLC38A4 gene is associated with hyperglycaemia. Copyright © 2012 John Wiley & Sons, Ltd. [PUBLICATION ABSTRACT]