HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

Giuffrida, Fernando de Mello Almada; Furuzawa, Gilberto K.; Kasamatsu, Teresa S.; Oliveira, Marcos Moraes; Reis, André; Dib, Sérgio Atala

doi:10.1186/1475-2840-8-28

Cited by 21 publications

(23 citation statements)

References 38 publications

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“…Knockout mice without the ApoA5 gene led to increased plasma TG, whereas its overexpression resulted in a reduction of TG . By contrast, one cross‐sectional study with a sample of Brazilian diabetic individuals demonstrated that the presence of the I27L variant can show a ‘protective effect’ with respect to the risk of hypertriglyceridemia . Thus, differences in genetic traits among studied populations or statistical methodology are a possible explanation for the association of the variants in the HNF1A and serum lipid levels.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 By contrast, one cross-sectional study with a sample of Brazilian diabetic individuals demonstrated that the presence of the I27L variant can show a 'protective effect' with respect to the risk of hypertriglyceridemia. 16 Thus, differences in genetic traits among studied populations or statistical methodology are a possible explanation for the association of the variants in the HNF1A and serum lipid levels. We could not exclude the possibility that the HNF1A was in LD with a functional variant of another gene on chromosome 12 that had been found in association with TG in GWAS.…”

Section: Interactions Of the Haplotypes And Environment Factors On mentioning

confidence: 99%

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Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke

Zhou

Yin

Shi

et al. 2017

The Journal of Gene Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Interactions Of the Haplotypes And Environment Factors On mentioning

confidence: 99%

Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke

Zhou

Yin

Shi

et al. 2017

The Journal of Gene Medicine

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“…Furthermore, some other gene polymorphisms such as hepatocyte nuclear factor-1 homeobox A (HNF1A) gene polymorphisms [11], PPARgamma gene C161T polymorphism [12] and adiponectin receptor-2 gene variations [13] have also been proved to be connected with diabetes and cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population

Chen

Yin

et al. 2010

Cardiovasc Diabetol

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BackgroundFour single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in KCNQ1 are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent. We investigated whether these 4 genetic markers are associated with serum lipid metabolism in a middle-aged Chinese Han population.MethodsWe enrolled 398 consecutive patients, including 180 with premature coronary artery disease (CAD) (male < 55 years, female < 65 years) and 218 controls without documented CAD. All subjects were genotyped for 4 SNPs by using the ligase detection reaction method. Fasting blood sugar (FBS) and plasma concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(apo A1), and apolipoprotein B (apo B) were determined by standard biochemical methods. Main anthropometric and metabolic characteristics are analyzed among 3 genotypes at rs2283228, rs2237895, rs2237897, or rs2237892 in KCNQ1.ResultsThe 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, and TT were present in rs2237897 and rs2237892. The minor genotypes CC at rs2283228 and TT at rs2237892 were associated with higher levels of TG (P = 0.007 and 0.026, respectively). Furthermore, subjects with the CC genotype at rs2283228 had lower levels of HDL-C and apo A1 than in the other 2 genotype groups (P = 0.052 and 0.055, respectively). No other associations were detected between these 4 SNPs and FBS or other lipid parameters.ConclusionsOur data suggest that rs2283228 and rs2237892 in KCNQ1 are associated with lipid metabolism in a middle-aged Chinese Han population.

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“…Mutations in the HNF1A gene (OMIM 142410) are the most common cause of MODY (Shields et al 2010). Furthermore, three frequent polymorphisms (I27L, A98V, and S487N) have been described in patients with T2D (Holmkvist et al 2006;Giuffrida et al 2009;Bonatto et al 2012). Characteristics of MODY carriers are:…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis of c.422_423InsT, a novel mutation of the HNF1A gene in a patient with diabetes

Magaña-Cerino

Luna-Arias

Labra-Barrios

et al. 2016

Molec Gen & Gen Med

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Background HNF1A gene regulates liver‐specific genes, and genes that have a role in glucose metabolism, transport, and secretion of insulin. HNF1A gene mutations are frequently associated with type 2 diabetes. HNF1A protein has three domains: the dimerization domain, the DNA‐binding domain, and the trans‐activation domain. Some mutations in the dimerization or DNA‐binding domains have no influence on the normal allele, while others have dominant negative effects. The I27L, A98V, and S487N polymorphisms are common variants of the HNF1A gene; they have been found in T2D and non‐diabetic subjects.Methods and ResultsWe searched for mutations in the first three exons of the HNF1A gen in an Amerindian population of 71 diabetic patients. DNA sequencing revealed the previously reported I27L polymorphism (c.79A>C) in 53% of diabetic patients and in 67% of the control group. Thus, the I27L/L27L polymorphism might be a marker of Amerindians. In addition, we found the c.422_423InsT mutation in the HNF1A gene of one patient, which had not been previously reported. This mutation resulted in a frame shift of the open reading frame and a new translation stop in codon 187, leading to a truncated polypeptide of 186 amino acids (Q141Hfs*47). This novel mutation affects the DNA‐binding capacity of the mutant HNF1A protein by EMSA; its intracellular localization by fluorescence and confocal microscopy, and a dominant‐negative effect affecting the DNA‐binding capacity of the normal HNF1A by EMSA. We also studied the homology modeling structure to understand the effect of this mutation on its DNA‐binding capacity and its dominant negative effect.ConclusionThe HNF1A Q141Hfs*47 mutant polypeptide has no DNA‐binding capacity and exerts a dominant negative effect on the HNF1A protein. Therefore, it might produce severe phenotypic effects on the expression levels of a set of β‐cell genes. Consequently, its screening should be included in the genetic analysis of diabetic patients after more functional studies are performed.

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HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

Cited by 21 publications

References 38 publications

Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke

Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke

KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population

Identification and functional analysis of c.422_423InsT, a novel mutation of the HNF1A gene in a patient with diabetes

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