<i>CRY2</i> (rs11605924) and <i>G6PC2</i> (rs560887) single nucleotide polymorphisms increase risk of type 2 diabetes mellitus

Single nucleotide polymorphisms (SNPs) are genetic risk factors for type 2 diabetes (T2D). SNPs of the cryptochrome circadian regulator 2 (<i>CRY2</i>), hepatocyte nuclear factor 1α, prospero homeobox 1 and glucose-6-phosphatase catalytic subunit (<i>G6PC2</i>) genes are associated with T2D. To the best of our knowledge, however, the association is unclear in African patients and the burden of T2D is growing rapidly in Africa. The present study aimed to investigate SNPs of cryptochrome circadian regulator 2 (<i>CRY2</i>), hepatocyte nuclear factor 1α, prospero homeobox 1 and glucose-6-phosphatase catalytic subunit (<i>G6PC2</i>) genes in T2D in a South African population. The study included 310 participants with T2D and 310 healthy controls. Demographic and lifestyle characteristics were self-reported, while anthropometric and biochemical measurements were determined using standard methods. Plasma glucose and insulin were measured by enzymatic hexokinase method and paramagnetic particle chemiluminescence assay, respectively. Highly sensitive c-reactive protein (hs-CRP) was measured by ELISA. iPLEX SNP genotyping was used for SNP analysis and results were confirmed by Sanger sequencing. Insulin resistance measured using the homeostasis model assessment of insulin resistance (HOMA-IR) formula was significantly higher in carriers of the recessive rs11605924 (P=0.049), fasting plasma glucose was significantly lower in carriers of the recessive rs560887 (P=0.015) and highly sensitive c-reactive protein levels were significantly lower in carriers of the recessive rs1169288 (P=0.018). The risk of T2D was significantly higher in participants with the recessive rs560887 [odds ratio (OR)=1.58, 95% CI, 1.02-2.44, P=0.041) and rs11605924 (OR=1.82, 95% CI, 1.03-3.23, P=0.041) compared with the dominant alleles. <i>CRY2</i> and <i>G6PC2</i> SNPs were associated with an increased risk of T2D and may partly contribute to high prevalence of T2D in the mixed ancestry South African population. Further studies are warranted to validate these findings in other African populations and explore downstream pathways.