The KLF14 Variant is Associated with Type 2 Diabetes and HbA1C Level

Abstract

The purpose of this study was to scan variants in coding region of Krȕppel like factor14 (KLF14) locus and assess association related to type 2 diabetes (T2D) in Iranian population. We sequenced the coding region of KLF14 to scan variants in case–sibling study (92 individuals with T2D and 92 healthy older siblings). To confirm, we analyzed rs76603546 association with T2D in a larger unrelated case–control study by PCR–RFLP (475 cases and 512 controls). We analyzed the association of rs76603546 with HbA_1C, BMI, fat mass, waist circumference, fasting glucose, cholesterol and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) using one-way ANOVA analysis. Also, association of genotypes with T2D adjusted for confounding variables was analyzed using logistic regression. HaploReg v 4.1 was used to predict rs76603546 possible function. Sequencing results analysis revealed the association of C allele of rs76603546, synonymous variant C>T, [OR 2.10 (1.38–3.20), P value < 0.001] and CC genotype of rs76603546 [OR 4.3 (1.79–10.23), P value = 0.001] with susceptibility to T2D. PCR-Restriction Fragment Length Polymorphism (RFLP) results analysis confirmed the association of rs76603546 with T2D [C allele, OR 1.91 (1.59–2.29), P value = 0.002, CC genotype, OR 3.27 (2.26–4.73), P value = 0.002 and TC genotype, OR 1.74 (1.31–2.31), P value = 0.001]. The CC genotype of rs76603546 is associated with HbA_1C level (P value < 0.001) and BMI (P value = 0.02). After adjustment with confounding variables, we observed association of CC genotype with T2D [OR 2.542 (1.25–3.77), P value = 0.03]. Among over 220 SNPs, rs76603546 was associated with T2D, HbA_1C and BMI in our study.