Taken together, our results suggest that methylation changes of Klf14 in those tissues may be associated with changes in gene expression and inflammation on the adipose tissue of obesity and T2D.
We show that carriers of the KLF14T2D risk allele shift body fat from gynoid stores to abdominal stores and display a marked increase in adipocyte cell size, and that these effects on fat distribution, and the T2D association, are female specific.
We discuss a recent study that has identified and validated the link between a type-2 diabetes (T2D) association and human adipose biology by means of KLF14 gene expression.
We show that carriers of the KLF14T2D risk allele shift body fat from gynoid stores to abdominal stores and display a marked increase in adipocyte cell size, and that these effects on fat distribution, and the T2D association, are female specific.
From the molecular function aspect, this review focuses on the impact of KLF14-mediated regulation in major atherosclerosis-related diseases and pathological processes, such as insulin resistance, type 2 diabetes, dyslipidemia, inflammation, obesity, metabolic syndrome, cell proliferation and differentiation.
The transcription factor Krüppel-like factor 14 (KLF14) has been associated with type 2 diabetes and high-density lipoprotein-cholesterol (HDL-C) through genome-wide association studies.
Despite strong evidence showing that a polymorphism in the <i>Klf14</i> gene is closely linked to the development of type 2 diabetes, the physiological and metabolic functions of KLF14 still remain unclear.
Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China.
The T2D risk alleles of rs972283 near KLF14 and rs11634397 near ZFAND6 were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), P = 1.46 × 10-2; rs11634397: 1.14 (1.00, 1.29), P = 4.66 × 10-2), while the T2D risk alleles of rs780094 in GCKR and rs7903146 in TCF7L2 were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), P = 1.35 × 10-4; rs7903146: 0.82 (0.69, 0.98), P = 3.18 × 10-2).
Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05).
Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression.
The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05).
We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians.