Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes.

ABSTRACT

BACKGROUND AND AIM: Based on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM). METHODS AND RESULT: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d181/160), Cer(d181/180), Cer(d181/200), Cer(d181/220), Cer(d181/240) and Cer(d181/241)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system. Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d181/180) (0.159 ± 0.05 vs. 0.120 ± 0.04 µmol/L, p = 0.012), Cer(d181/200) (0.129 ± 0.04 vs. 0.098 ± 0.03 µmol/L, p = 0.008), and Cer(d181/241) (1.236 ± 0.38 vs. 0.978 ± 0.36 µmol/L, p = 0.032) compared with those with C/C genotype. CONCLUSIONS: The C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.