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

Shahvazian, Ensieh; Mahmoudi, Mohammad; Yazd, Ehsan Farashahi; Gharibi, Saba; Moghimi, Bahram; HosseinNia, Pouria; Mirzaei, Masoud

doi:10.1007/s10528-020-10015-w

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…It was commonly agreed that these genes regulate many types of cellular processes such as apoptosis, metabolism, proliferation, and differentiation ( Lomberk and Urrutia, 2005 ). Some GWAS results also disclosed that genetic variants surrounding the KLF14 gene are closely linked to type 2 diabetes, HDL-C levels, metabolic syndrome, HbA1C, and atherosclerosis ( Teslovich et al, 2010 ; Small et al, 2011 ; Chen et al, 2012 ; Elouej et al, 2016 ; Shahvazian et al, 2021 ). Recently discovered as belonging to the KLF family, KLF14 was found to regulate cholesterol efflux through inhibiting inflammatory response in macrophages and the expression of ABCA1 ( Wang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

APOE and KLF14 genetic variants are sex-specific for low high-density lipoprotein cholesterol identified by a genome-wide association study

et al. 2022

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To demonstrate the loci that relate to high-density lipoprotein cholesterol (HDL-C) levels and genetic sex heterogeneity, we enrolled 41,526 participants aged between 30 and 70 years old from the Taiwan Biobank in a genome-wide association study. We applied the Manhattan plot to display the p-values estimated for the relationships between loci and low HDL-C. A total of 160 variants were significantly associated with low HDL-C. The genotype TT of rs1364422 located in the KLF14 gene has 1.30 (95% CI=1.20 -1.42) times the risk for low-HDL compared to genotype CC in females (log(-p) =8.98). Moreover, the genes APOC1, APOE, PVRL2, and TOMM40 were associated significantly with low-HDL-C in males only. Excluding the variants with high linkage disequilibrium, we revealed the rs429358 located in APOE as the major genetic variant for lowering HDL-C, in which genotype CT has 1.24 (95% CI= 1.16 -1.32) times the risk. In addition, we also examine 12 genes related to HDL-C in both sexes, including LPL, ABCA1, APOA5, BUD13, ZPR1, ALDH1A2, LIPC, CETP, HERPUD1, LIPG, ANGPTL8, and DOCK6. In conclusion, low-HDL-C is a genetic and sex-specific phenotype, and we discovered that the APOE and KLF14 are specific to low-HDL-C for men and women, respectively.

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Section: Discussionmentioning

confidence: 99%

APOE and KLF14 genetic variants are sex-specific for low high-density lipoprotein cholesterol identified by a genome-wide association study

et al. 2022

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“…One of the studies suggested that the increased propensity of consanguineous marriage is a strong genetic component that exists in T2DM [ 18 ]. Genetic polymorphisms that influence the beta cells in insulin release and secretion such as gene TCF7L2 locus rs7901695 and rs7903146, gene KCNQ1 locus rs2237892, rs7756992, and gene CDKAL1 locus rs7754840 and KLF14 variant [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Consanguinity and Diabetes in Saudi Population: A Case-Control Study

Alzahrani¹,

Alzahrani²,

jabir³

et al. 2021

Cureus

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Background and Aim: Diabetes mellitus (DM) of both types is a genetically determined disorder and is prevalent in the Saudi population. Furthermore, the rate of consanguineous marriages is also high among Saudis. Therefore, we aimed to determine the prevalence of consanguinity among people with DM and investigate the effect of consanguinity on the occurrence of diabetes at different levels. Methods: A descriptive cross-sectional study was carried out at the Obesity, Metabolism and Endocrine Center of King Fahad Medical City in Riyadh, Saudi Arabia in January 2021. Information on patients’ demographics (age, gender), family history of DM, and presence of consanguinity, and degree of consanguineous marriage were collected. Results: We included 324 people with DM, 143 (44.1%) with type 1 diabetes (T1DM), and 181 (55.9%) with type 2 diabetes (T2DM). We included 201 people without DM for T1DM control and 300 people for T2DM control. The mean age was 26.6 ± 11.1 years for the T1DM group and 57.8 ± 11.6 years for the T2DM group. Consanguinity was noted among 73 (51.4%) T1DM patients, but T1DM was not significantly related to consanguinity. T2DM was significantly correlated with consanguinity (r=0.132, p=0.004) particularly among patients with a degree of consanguinity as first-cousins for both paternal and maternal sides (odds ratio [OR]=1.151 and 1.476). Gender and positive family history for DM and consanguineous marriage between cousins were significant factors for T2DM. After controlling for gender and a positive family history of DM, consanguineous marriage between cousins from both the paternal and maternal sides remained significant. Conclusion: T2DM occurrence increases in presence of consanguinity in the Saudi population. This relationship might contribute to the higher risk of DM prevalence. Further studies are needed to elucidate this relationship deeply. It’s unclear whether lowering consanguineous marriages would decrease the prevalence of diabetes or not. However, a clear message about this correlation has to be delivered to the public.

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“…A logistic regression model was used to analyze the association between genotypes and T2DM, adjusted for body height, BMI, Hb1Ac, and body weight. This investigational study reported the KLF14 rs76603546 association with Hb1Ac and T2DM in the targeted population [ 80 ].…”

Section: Single Nucleotide Polymorphisms Of Klf14mentioning

confidence: 99%

Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms

et al. 2023

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Krüpple-Like family of transcription factor-14 (KLF14) is a master trans-regulatory gene that has multiple biological regulatory functions and is involved in many pathological mechanisms. It controls the expressions of several other genes which are involved in multiple regulatory functions. KLF14 plays a significant role in lipid metabolism, glucose regulation and insulin sensitivity. Cell apoptosis, proliferation, and differentiation are regulated by the KLF14 gene, and up-regulation of KLF14 prevents cancer progression. KLF14 has been used as an epigenetic biomarker for the estimation of chronological age due to the presence of different age-related CpG sites on genes that become methylated with age. Different genome-wide association studies have identified several KLF14 variants in adipose tissues. These single nucleotide polymorphisms in KLF14 have been associated with dyslipidemia, insulin resistance, and glucose intolerance. Moreover, the prevalence of genetic polymorphism is different in different populations due to ethnic differences and epigenetic modifications. In addition, environmental and physiological factors such as diet, age, gender, and obesity are also responsible for genetic mutations in KLF14.

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

Cited by 6 publications

References 40 publications

APOE and KLF14 genetic variants are sex-specific for low high-density lipoprotein cholesterol identified by a genome-wide association study

APOE and KLF14 genetic variants are sex-specific for low high-density lipoprotein cholesterol identified by a genome-wide association study

Consanguinity and Diabetes in Saudi Population: A Case-Control Study

Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms

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