Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus

Abstract EN

Nuclear factor-Y (NF-Y) consists of three evolutionary conserved subunits including NF-YA, NF-YB, and NF-YC; it is a critical transcriptional regulator of lipid and glucose metabolism and adipokine biosynthesis that are associated with type 2 diabetes mellitus (T2DM) occurrence, while the impacts of genetic variants in the NF-Y gene on the risk of T2DM remain to be investigated.

In the present study, we screened five single-nucleotide polymorphisms (SNPs) with the SNaPshot method in 427 patients with T2DM and 408 healthy individuals.

Subsequently, we analyzed the relationships between genotypes and haplotypes constructed from these SNPs with T2DM under diverse genetic models.

Furthermore, we investigated the allele effects on the quantitative metabolic traits.

Of the five tagSNPs, we found that three SNPs (rs2268188, rs6918969, and rs28869187) exhibited nominal significant differences in allelic or genotypic frequency between patients with T2DM and healthy individuals.

The minor alleles G, C, and C at rs2268188, rs6918969, and rs28869187, respectively, conferred a higher T2DM risk under a dominant genetic model, and the carriers of these risk alleles (either homozygotes of the minor allele or heterozygotes) had statistically higher levels of fasting plasma glucose, cholesterol, and triglycerides.

Haplotype analysis showed that SNPs rs2268188, rs6918969, rs28869187, and rs35105472 formed a haplotype block, and haplotype TTAC was protective against T2DM (OR=0.76, 95% CI=0.33-0.82, P=0.004), while haplotype GCCG was associated with an elevated susceptibility to T2DM (OR=2.33, 95% CI=1.43-3.57, P=0.001).

This study is the first ever observation to our knowledge that indicates the genetic variants of NF-YA might influence a Chinese Han individual’s occurrence of T2DM.