Abstract
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.
Highlights
Type 2 diabetes mellitus (T2DM), accounting for more than 90% of all cases of diabetes, is increasing rapidly and becoming a major public health threat throughout the world
We recently found that the NF-YA liver-specific knockout mice showed significantly reduced blood glucose levels; further evidences demonstrated that NF-YA controls glucose production mainly through upregulating the gluconeogenic enzyme expression, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose6-phosphatase catalytic subunit (G6Pase) [13]
We examined the relationships between five tagSNPs in the NF-YA region and their susceptibilities to T2DM
Summary
Type 2 diabetes mellitus (T2DM), accounting for more than 90% of all cases of diabetes, is increasing rapidly and becoming a major public health threat throughout the world. Owing to the importance of the CCAAT motif in gene transcription and the critical roles of NF-Y in numerous biological processes, there is a significant number of investigations developing agents that alter NF-Y DNA-binding pattern or its activity. The synthetic antitumor agent HNM-176 can suppress the expression of multidrug resistance gene (MDR1) by inhibiting NF-Y activity in cancer cell lines [16] Histone deacetylase inhibitors, such as trichostatin A, vorinostat, and valproic acid, clearly alter NF-Y activity via the impact on its acetylation [17, 18]. It is therapeutically feasible to modulate NF-Y activity through designing proper compounds This strengthens the importance of assessing whether NF-Y may be a risk gene of T2DM. This aim of the present study was to examine the relationship between genetic variants in NF-YA gene with a T2DM risk in a Chinese Han population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
