Association of Genetic Variants with Isolated Fasting Hyperglycaemia and Isolated Postprandial Hyperglycaemia in a Han Chinese Population

<div><p>Background</p><p>Though multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes have been identified, the genetic bases of isolated fasting hyperglycaemia (IFH) and isolated postprandial hyperglycaemia (IPH) were still unclear. In present study, we aimed to investigate the association of genome-wide association study-validated genetic variants and IFH or IPH in Han Chinese.</p><p>Methods/Principal Findings</p><p>We genotyped 27 validated SNPs in 6,663 unrelated individuals comprising 341 IFH, 865 IPH, 1,203 combined fasting hyperglycaemia and postprandial hyperglycaemia, and 4,254 normal glycaemic subjects of Han ancestry. The distributions of genotype frequencies of <i>FTO</i>, <i>CDKAL1</i> and <i>GCKR</i> were significant different between individuals with IFH and those with IPH (SNP(<i>p_trend</i>): rs8050136(0.0024), rs9939609(0.0049), rs7756992(0.0122), rs780094(0.0037)). Risk allele of <i>FTO</i> specifically increased the risk of IFH (rs8050136: OR 1.403 [95% CI 1.125–1.750], <i>p</i> = 0.0027; rs9939609: 1.398 [1.120–1.744], <i>p</i> = 0.0030). G allele of <i>CDKAL1</i> specifically increased the risk of IPH (1.217 [1.092–1.355], <i>p</i> = 0.0004). G allele of <i>GCKR</i> increased the risk of IFH (1.167 [0.999–1.362], <i>p</i> = 0.0513), but decreased the risk of IPH (0.891 [0.801–0.991], <i>p</i> = 0.0331). In addition, <i>TCF7L2</i> and <i>KCNQ1</i> increased the risk of both IFH and IPH. When combined, each additional risk allele associated with IFH increased the risk for IFH by 1.246-fold (<i>p</i><0.0001), while each additional risk allele associated with IPH increased the risk for IPH by 1.190-fold (<i>p</i><0.0001).</p><p>Conclusion/Significance</p><p>Our results indicate that genotype distributions of variants from <i>FTO, GCKR</i>, <i>CDKAL1</i> were different between IPH and IFH in Han Chinese. Variants of genes modulating insulin sensitivity (<i>FTO</i>, <i>GCKR</i>) contributed to the risk of IFH, while variants of genes related to beta cell function (<i>CDKAL1</i>) increase the risk of IPH.</p>