KCNJ11 and KCNQ1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes Mellitus

Majcher, Sandra; Ustianowski, Przemysław; Malinowski, Damian; Czerewaty, Michał; Tarnowski, Maciej; Safranow, Krzysztof; Dziedziejko, Violetta; Pawlik, Andrzej

doi:10.3390/genes13081315

Cited by 5 publications

(7 citation statements)

References 30 publications

(40 reference statements)

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“…For example, the frequency of this allele is 10.5% in Malaysia [ 45 ], 3.3% in South Korea [ 46 ], 2% in China [ 29 ], 36.4% in Qatar [ 47 ], 33% in Poland [ 25 ], 36.2% in Spain [ 48 ], 74% in Lithuania [ 49 ], 38.8% in India, 24% in Bangladesh [ 50 ], 23% in Mexico [ 27 ], 48.4% in Australia [ 51 ], and 27.6% in Denmark [ 52 ]. The MAF of the rs2237892 SNP in this population was determined to be 9%, with a prevalence of 8.3% in Poland [ 35 ], which is quite close to our study. The populations of other countries were documented as 34% [ 32 ] and 34.2% [ 53 ] in Korea, 36% in Japan [ 54 ], and 28.9% [ 44 ] and 27.8% [ 55 ] in China.…”

Section: Discussionsupporting

confidence: 88%

“…Replication of case-control studies was carried out in different populations of women with GDM among the rs7903146 [ 25 , 26 , 27 , 28 , 29 , 30 ], rs2237892 [ 31 , 32 , 33 , 34 , 35 ], and rs5219 [ 35 , 36 , 37 , 38 ] SNPs. Meta-analysis studies have been carried out with rs7903146 [ 39 , 40 , 41 , 42 , 43 ], rs2237892 [ 42 , 44 ] and rs5219 SNPs [ 42 ] in women with GDM.…”

Section: Discussionmentioning

confidence: 99%

“…The rs5219 SNP was found in our study at a rate of 22%, which is comparable to that in the Greek population of 20.9% [ 56 ]. The prevalence was 26% [ 38 ] and 38% [ 57 ] in the Indian population, 36.5% in the Polish population [ 35 ], 59.3% in the Russian population [ 36 ], 40% in the Danish population [ 52 ], and 42.2% in the Swedish population [ 58 ]. However, rs7903146 SNP was not associated in T2DM subjects from Eastern provenience region in Saudi Arabia.…”

Section: Discussionmentioning

confidence: 99%

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Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Alshammary

Al-Hakeem

Khan

2023

Genes

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Background: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic β-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the mechanism of β-cell dysfunction. The purpose of this study was to investigate the genes associated with β-cell dysfunction and their genetic roles in the rs7903146, rs2237892, and rs5219 variants in Saudi women diagnosed with type 2 diabetes mellitus and GDM. Materials and Methods: In this case-control study, 100 women with GDM and 100 healthy volunteers (non-GDM) were recruited. Genotyping was performed using polymerase chain reaction (PCR), followed by restriction fragment length analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed using multiple software packages. Results: Clinical studies showed a β-cell dysfunction positive association in women with GDM when compared to non-GDM women (p < 0.05). Both rs7903146 (CT vs. CC: OR-2.12 [95%CI: 1.13–3.96]; p = 0.01 & T vs. C: (OR-2.03 [95%CI: 1.32–3.11]; p = 0.001) and rs5219 SNPs (AG vs. AA: OR-3.37 [95%CI: 1.63–6.95]; p = 0.0006 & G vs. A: OR-3.03 [95%CI: 1.66–5.52]; p = 0.0001) showed a positive association with genotype and allele frequencies in women with GDM. ANOVA analysis confirmed that weight (p = 0.02), BMI (p = 0.01), and PPBG (p = 0.003) were associated with rs7903146 and BMI (p = 0.03) was associated with rs2237892 SNPs. Conclusions: This study confirms that the SNPs rs7903146 (TCF7L2) and rs5219 (KCNJ11) are strongly associated with GDM in the Saudi population. Future studies should address the limitations of this study.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Alshammary

Al-Hakeem

Khan

2023

Genes

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“…Women who initially develop diabetes during pregnancy, due to carbohydrate intolerance with no established DM diagnosis, are diagnosed with GDM. The pathogenesis of GDM includes pancreatic β-cell failure caused by placental and genetic factors [4]. Advanced maternal age, elevated weight gain during pregnancy, metabolic inflammation, nutritional deficiency, increased adipose tissue, physical inactivity, oxidative stress, polycystic ovary syndrome (PCOS), the infant born weighing 4 kg plus, a family history of T2DM, and GDM are the major common risk factors for developing GDM during pregnancy [5].…”

Section: Introductionmentioning

confidence: 99%

Relevance of Serum Levels and Functional Genetic Variants in Vitamin D Receptor Gene among Saudi Women with Gestational Diabetes Mellitus

Ali Khan,

Alhaizan,

Neyazi

et al. 2023

Nutrients

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Background: This study explored the association between ApaI–TaqI Single Nucleotide Polymorphisms (SNPs) in a Vitamin D receptor (VDR) and the risk of Gestational Diabetes Mellitus (GDM) in Saudi women, along with the serum levels of vitamin D. Methods: Ninety women with GDM and 90 non-GDM women were enrolled, based on the inclusion and exclusion criteria for pregnant women enrolled in a single-center study. Blood samples were retrieved from 180 pregnant women using ethylenediaminetetraacetic acid (EDTA) tubes. Serum samples were used to measure the vitamin D, 25-hydroxyvitamin D (25(OH)D or calcidiol), and lipid profiles. Blood was used to measure the hemoglobin A1c levels and to isolate the DNA. The polymerase chain reaction (PCR) was performed for the ApaI (rs79785232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236) SNPs in the VDR gene using restriction fragment length polymorphism analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed between the patients with and without GDM using various statistical software packages. Results: The Hardy–Weinberg equilibrium analysis was statistically significant (p > 0.05). The ApaI, BsmI, and TaqI SNPs were associated with alleles, genotypes, and different genetic models (p < 0.05). Vitamin D levels were associated with deficient levels (p = 0.0002), as well as with a normal and overweight body mass index (p = 0.0004). When vitamin D levels were measured with GDM covariates, the fasting plasma glucose (FPG) (p = 0.0001), postprandial blood glucose (PPBG) (p < 0.0001), oral glucose tolerance test (OGTT)-1 h (p = 0.005), high-density lipoprotein (p = 0.022), and low-density lipoprotein cholesterol (LDLc) (p = 0.001) levels were significantly different. When similar vitamin D levels were measured for each genotype, we confirmed that the ApaI SNP was associated with sufficient levels (p < 0.0001), whereas the BsmI, FokI, and TaqI (p < 0.05) were associated with insufficient levels. The logistic regression model confirmed that the first hour of the OGTT (p = 0.005) was strongly associated with GDM, whereas the analysis of variance confirmed that FPG and PPBG (p < 0.05) were strongly associated with all the SNPs evaluated in the VDR gene. Additionally, the second hour of the OGTT (p = 0.048) and LDLc (p = 0.049) were associated with the ApaI and FokI SNP. Moreover, the first hour OGTT (p = 0.045) and lipid profile parameters (p < 0.05) were associated. Haplotype analysis revealed positive associations among the examined SNPs, which seemed compatible with the hypothesis that variants and combinations of multiple SNP genotypes enhance the risk of GDM in women. Haplotype analysis revealed that different combinations of alleles, such as AGCC, CATT, CGTC, AGTC, and CATT (p < 0.05), were strongly associated. The linkage disequilibrium (LD) analysis showed a strong association with all combinations (p < 0.05). Among the gene–gene interactions, all possible combinations showed a positive association (p < 0.05). Conclusions: Low vitamin D levels were observed in women with GDM. The ApaI, BsmI, and TaqI SNPs were associated with genotype and allele frequencies (p < 0.05). Vitamin D and the SNPs in the VDR gene were associated, according to the ANOVA, logistic regression, haplotype analysis, LD analysis, and the generalized multifactor dimensionality reduction model (p < 0.05).

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“…Distribution of THADA, SDHAF4, and MACF1 genotypes and alleles in women with GDM and the control group[21][22][23].…”

mentioning

confidence: 99%

THADA, SDHAF4, and MACF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

Ustianowski

Malinowski

Czerewaty

et al. 2022

Genes

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Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnant women leading to various complications. Consequently, factors predisposing its development are being sought. Previous studies have shown that the pathogenesis of GDM is similar to that of type 2 diabetes, and it is therefore thought that the two diseases may have a common genetic basis. The aim of this study was to examine the associations between thyroid adenoma-associated (THADA) rs7578597 T>C, succinate dehydrogenase complex assembly factor 4 (SDHAF4) rs1048886 A>G, and microtubule-actin crosslinking factor 1 (MACF1) rs2296172 A>G gene polymorphisms and the risk of GDM development as well as selected clinical parameters in women with GDM. We also examined the expression of these genes in the placenta of women with and without GDM in association with clinical parameters. This case-control study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. There were no statistically significant differences in the distribution of the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms between pregnant control women and women with GDM. The associations between clinical parameters such as body mass before pregnancy, body mass at birth, body mass increase during pregnancy, BMI before pregnancy, BMI at birth, BMI increase during pregnancy, glycated hemoglobin (HbA1c), daily insulin requirement, childbirth time, and newborn body mass and APGAR score, and the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G genotypes were statistically non-significant. We only observed lower values of body mass before pregnancy and body mass at birth in women with the SDHAF4 rs1048886 AG genotype in comparison with AA genotype carriers. There was no statistically significant difference in the expression of THADA, SDHAF4, and MACF1 genes in the placenta between women with GDM and healthy women. There were also no statistically significant correlations between THADA, SDHAF4, and MACF1 gene expression in the placenta and clinical parameters. The results of our study suggest that THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms are not significant factors associated with GDM onset. In addition, SDHAF4 rs1048886 A>G may be associated with body mass before pregnancy and body mass at birth in pregnant women.

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KCNJ11 and KCNQ1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes Mellitus

Cited by 5 publications

References 30 publications

Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Relevance of Serum Levels and Functional Genetic Variants in Vitamin D Receptor Gene among Saudi Women with Gestational Diabetes Mellitus

THADA, SDHAF4, and MACF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

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