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Author: search.filters.author.Eyerci, Nilnursearch.filters.applied.f.language: search.filters.language.eng

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    Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus
    (2019) Beysel, Selvihan; Eyerci, Nilnur; Ulubay, Mustafa; Caliskan, Mustafa; Kizilgul, Muhammed; Hafizoglu, Merve; Cakal, Erman; 31114636
    IntroductionPre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women.Patients and methodsWomen with GDM (n=160) and without GDM (n=145) were included in case-controlled study. Genotyping of the HNF1A gene (p.I27L rs1169288, p.98V rs1800574, p.S487N rs2464196), the VDR gene (p.BsmI rs1544410, p.ApaI rs7975232, p.TaqI rs731236, p.FokI rs2228570), and FTO gene (rs9939609) SNPs were performed by using RT-PCR.ResultsThe FTO AA genotype was associated with an increased risk of having GDM (AA vs. AT+TT, 24.4% vs. 12.4%, OR=2.27, 95% CI [1.23-4.19], p=0.007). The HNF1A p.I27L GT/TT genotype was associated with increased GDM risk (GT+TT vs. GG-wild, 79.4% vs. 65.5%, OR=2.02, 95% CI 1.21-3.38], p=0.007). However, all VDR gene SNPs and the HNF1A p.A98V, p.S487N were not associated with having GDM (p>0.05). The FTO AA genotype was associated with an increased risk for pre-pregnancy overweight/obesity (OR=1.43, 95% CI [1.25-3.4], p=0.035), but not associated with excessive GWG after adjusting for pre-pregnancy weight (p>0.05). Pre-pregnancy weight, weight at delivery, and GWG did not differ in both VDR and HNF1A gene carriers (p>0.05). HOMA-IR and HbA1c were increased in both p.I27L TT and FTO AA genotype carriers (p<0.05).ConclusionThe adiposity-related gene FTO is associated with GDM by the effect of FTO on pre-pregnancy obesity. The diabetes-related p.I27L gene is associated with GDM by increasing insulin resistance.
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    The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women
    (2019) Apaydin, Mahmut; Beysel, Selvihan; Eyerci, Nilnur; Pinarli, Ferda Alparslan; Ulubay, Mustafa; Kizilgul, Muhammed; Ozdemir, Ozhan; Caliskan, Mustafa; Cakal, Erman; 31096931
    BackgroundThe association between the vitamin D receptor (VDR) gene and gestational diabetes mellitus (GDM) has not been investigated in Turkish pregnant women. We aimed to investigate associations between VDR gene BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) single nucleotide polymorphisms (SNPs) and GDM.Material-methodsThis case-control study comprised 100 women with GDM and 135 pregnant women without GDM. The VDR polymorphism was evaluated using Sanger-based DNA sequencing.ResultVDR gene ApaI, BsmI, and TaqI SNPs did not differ between women with and without GDM (each, p>0.05). ApaI, BsmI, and TaqI were not associated with GDM risk. The VDR gene FokI CT/TT genotype was associated with an increased GDM risk (CT vs. CC, OR=1.84, 95% CI: [1.05-3.23], p=0.031; TT vs. CC, OR=3.95, 95% CI: [1.56-9.96], p=0.002; CT/TT vs. CC, OR=2.29, 95% CI: [1.35-3.89], p=0.002; and CT/CC vs. TT, OR=3.02, 95% CI: [1.23-7.38], p=0.012). The FokI-TT genotype was more associated with younger age and higher glucose, HbA1c, and HOMA-IR than the CC and CT genotype. FokI-T was positively correlated with log-HOMA-IR (r=0.326, p=0.004). FokI SNPs were independently associated with GDM after adjusting for BMI and age (=1.63, 95% CI: [1. 2-4.2], p=0.012). There were no associations between the FokI, ApaI, BsmI and TaqI haplotypes and GDM.ConclusionVDR gene FokI SNPs were independently associated with having GDM in Turkish women. VDR gene FokI SNPs might contribute to insulin resistance of developing GDM.
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    HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey
    (2019) Beysel, Selvihan; Eyerci, Nilnur; Pinarli, Ferda Alparslan; Kizilgul, Muhammed; Ozcelik, Ozgur; Caliskan, Mustafa; Cakal, Erman; 31109344
    BackgroundThe molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population.MethodsAll diabetic patients (N=565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n=46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n=30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n=486) and non-diabetic controls (n=263) were included. Genetic analyses for the HNF1A gene p.S487N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group.Resultsp.S487N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p>0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR=1.68, 95% CI: [1. 21-2.13]; p=0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR=1.56, 95% CI: [1. 14-2.57]; p=0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (=1.45, 95% CI: [1. 2-4.2]; p=0.036).ConclusionsThe HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.
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    HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus
    (2019) Beysel, Selvihan; Pinarli, Ferda Alparslan; Eyerci, Nilnur; Kizilgul, Muhammed; Hepsem, Sema; Alhan, Ali; Kan, Seyfullah; Caliskan, Mustafa; Bozkurt, Erhan; Cakal, Erman; 31825269
    The association of the FTO gene and HNF1 alpha gene on gestational diabetes mellitus (GDM) and preeclampsia remains unclear. This is the first study to examine whether HNF1 alpha gene and FTO gene were associated with having GDM and preeclampsia in Turkish women. Healthy pregnant women (n = 101) and women with GDM (n = 169) were included. GDM was divided into two groups as GDM-only (n = 90) and GDM-preeclampsia (n = 79). Genotyping of HNF1 alpha gene p.I27L, p.A98V, and p.S487N, and FTO gene rs9939609 SNPs were performed using RT-PCR. The frequency of p.S487N, p.A98V, and FTO genotype were similar between the groups (p > .05). p.I27L GG-wild, GT, and TT genotype were 56.5%, 36.6%, and 6.9% in controls; 40.0%, 51.1%, and 8.9% in GDM-only; and 26.6%, 51.9%, and 21.5% in GDM-preeclampsia (p = .034). TT and GT genotype was more frequent in GDM-preeclampsia than in controls (p < .05). GT genotype was increased in GDM-only compared with controls (p < .05). TT genotype was more frequent in GDM-preeclampsia than in GDM-only (p < .05). p.I27L TT genotype was independently associated with increased blood pressure (BP) and urinary protein. p.I27L TT genotype was associated with increased preeclampsia risk in patients with GDM by increasing BP and urinary protein.