Hematopoietically expressed homeobox gene is associated with type 2 diabetes in KK Cg-Ay/J mice and a Taiwanese Han Chinese population

Abstract

Diabetes mellitus (DM) is a chronic disease. The KK Cg-A^y/J (KK-A^y) mouse is an animal model to study type 2 diabetes mellitus (T2D) disease. The present study assessed the expression of hematopoietically expressed homeobox (HHEX) protein in liver tissues of different age groups of mice (6, 16 and 42 weeks) by immunohistochemistry (IHC). The results demonstrated a significant decrease in the percentage of HHEX-positive cells in KK-A^y mice as compared with that in KK-α/α control mice. Furthermore, in Taiwan's Han Chinese population, genotypic and allelic frequency distributions of the rs61862780 single-nucleotide polymorphism (SNP) in the HHEX gene were investigated. The results demonstrated that in the rs61862780 SNP of the 3'-untranslated region (UTR) of HHEX, the frequency of the CC genotype was higher in patients (6.0%) than in controls (2.7%), while the TT genotype frequency was about equal. In the same SNP, the frequency of the C allele was higher in patients (21.0%) than in controls (17.3%), while the T allele frequency was about equal. These results may pave the road for exploring the KK-A^y mouse model and the HHEX SNP rs61862780, which was correlated with the susceptibility to T2D in a Chinese population. Based on these findings, an association of HHEX gene expression with pathological features of T2D was indicated.

Keywords: Chinese population; KK Cg-Ay/J mouse; hematopoietically expressed homeobox; single-nucleotide polymorphism; type 2 diabetes mellitus.

Figure 1.

Representative immunohistochemical images for detecting HHEX expression in the livers of KK Cg-A^y/J mice with T2D compared with that in normal KK-α/α mice (arrows indicate HHEX expression identified by brown staining; magnification, ×200 or ×400). HHEX, hematopoietically expressed homeobox; T2D, type 2 diabetes.

Figure 2.

Cartoon representation of HHEX protein expression in KK-α/α mice (normal mice; black color) and KK Cg-A^y/J mice (T2D mice; yellow color) depending on the age of the mice. The amount of HEXX expression is indicated by + symbols. HHEX, hematopoietically expressed homeobox; T2D, type 2 diabetes.