Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor‐1α gene and the relationship to β‐cell function during an OGTT in glucose‐tolerant women with and without previous gestational diabetes mellitus

Lauenborg, Jeannet; Damm, Peter; Ek, Jakob; Glümer, Charlotte; Jørgensen, Torben; Borch‐Johnsen, Knut; Vestergaard, Henrik; Hornnes, Peter; Pedersen, Oluf; Hansen, Torben

doi:10.1111/j.1464-5491.2004.01343.x

Cited by 17 publications

(9 citation statements)

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“…Interestingly, the G319S variant of HNF-1␣, a major susceptibility gene for type 2 diabetes in the Oji-Cree Native Canadian population, is also associated with a significantly lower age at onset of diabetes (23). However, in Danish (11) and Swedish (13) populations, no significant difference was seen in the allele/genotype frequency of the Ala/Val polymorphism when comparing type 2 diabetic patients with glucose-tolerant patients (11,12) or when comparing patients with gestational diabetes with glucose-tolerant patients (24). An earlier study on South Indians had shown an association of this polymorphism with type 2 diabetes (25), but it did not deal with MODY or with age at diagnosis of type 2 diabetes.…”

Section: Results -mentioning

confidence: 99%

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

et al. 2005

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OBJECTIVE—Among Europeans, mutations in the hepatocyte nuclear factor-1α (HNF1α) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1α gene in different types of diabetes in Asian Indians. RESEARCH DESIGN AND METHODS—Genotyping of Ala98Val was done by the PCR–restriction fragment–length polymorphism method in the following groups: 1) MODY, defined as non–insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups. RESULTS—The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2–like diabetes (groups 1–4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002). CONCLUSIONS—Among Asian Indians, the Ala98Val polymorphism of HNF1α gene is associated with MODY and with earlier age at onset of type 2 diabetes.

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Section: Results -mentioning

confidence: 99%

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

et al. 2005

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“…131 Finally, two variants within the HNF1A gene were investigated in association with gestational diabetes. The HNF1A Ala98Val polymorphism was not associated with gestational diabetes in a casecontrol study of 376 women with gestational diabetes and 1034 control subjects, 132 whereas the Leu27 allele of the Ile27Leu polymorphism was more common among a sample of 648 women with gestational diabetes compared with a sample of 1232 control women, but this result was of borderline significance (36.3% vs. 33.0%, OR:1.16, 95% CI: 1.001-1.34) and was not statistically significant after correction for multiple comparisons (P ϭ 0.17). 129 Several variants within HNF1A were compared between 119 white women with GDM and 120 pregnant nondiabetic controls, and no association was observed.…”

Section: Forkhead Box C2 (Foxc2)mentioning

confidence: 99%

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

Robitaille

Grant

2008

Genetics in Medicine

129

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Gestational diabetes is a major public health problem because of its prevalence, its associated complications during pregnancy, and its increased risk for type 2 diabetes later in life. Insulin resistance is one of many physiological changes occurring during pregnancy, and when insulin resistance is accompanied by pancreatic ␤-cell insufficiency, gestational diabetes may develop. Several lines of evidence suggest that gestational diabetes shares a common etiology with type 2 diabetes and support the hypothesis that gestational diabetes serves as a window to reveal a predisposition to type 2 diabetes. Pregnancy is an environmental stressor that may catalyze the progression to a diabetic state in genetically predisposed women; therefore, identification of these women during pregnancy could decrease the occurrence of type 2 diabetes through targeted prevention. This review presents an overview of the genetics of gestational diabetes, focusing on human association studies with candidate genes common to both type 2 diabetes and gestational diabetes. Genet Med 2008:10(4):240 -250. Key Words: gestational diabetes mellitus, type 2 diabetes, genetics, pregnancy, association studiesGestational diabetes mellitus (GDM) is a major public health problem because of its prevalence and its associated complications during pregnancy. It is estimated that 4% of pregnancies in the United States are complicated by GDM, although the prevalence of GDM varies considerably among racial and ethnic groups. 1 Uncontrolled GDM increases the risk of adverse neonatal outcomes such as macrosomia, birth injuries, neonatal hypoglycemia, neonatal cardiac dysfunction, and stillbirth. 2 In addition to increasing the risk of adverse infant outcomes, GDM also has high predictive value for later development of type 2 diabetes (T2D) in the mother and in her offspring. Women who experience GDM have increased risk of developing T2D after pregnancy, ranging from 17% to 63% within 5-16 years after pregnancy depending on the population and other risk factors. 3 Additionally, offspring of mothers with GDM are more likely to be obese and display impaired glucose tolerance during adolescence than are offspring of nondiabetic mothers. Thus, diabetes during pregnancy is not only associated with the later risk of diabetes in mothers but also with metabolic changes that may lead to the development of diabetes in their offspring. 4 This observed connection between GDM and risk of T2D strongly suggests that GDM can serve as a window revealing a predisposition to T2D, with pregnancy as the environmental stressor that catalyzes progression to a diabetic state in predisposed individuals. 5 Several lines of evidence support the above hypothesis. First, GDM shares several risk factors with T2D, including high body mass index (BMI), history of abnormal glucose tolerance, diabetes in a first-degree relative, and membership in an ethnic group with a high risk of T2D. 6 Second, GDM and T2D share similar pathophysiologies: women undergo major physiological changes during pregn...

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“…Glucose concentrations after fasting, and 1 and 2 h after glucose administration < 92 mg/dl, < 180 mg/dl, and < 153 mg/dl, respectively, were considered normal. When the pregnant women’s glucose concentration was higher than any of these values, the women were diagnosed as having GDM [12]. Women whose GDM was diagnosed according to these criteria, aged 22–38 years, and whose pregnancy age was 24–48 weeks were included in the study.…”

Section: Methodsmentioning

confidence: 99%

“…We aimed to examine whether these genetic variants would associate with having GDM, and then, whether the genetic variants that associated with GDM would associate with adiposity including pre-pregnancy obesity and excessive GWG. The VDR gene (encoding as SNPs p.BsmI, p.ApaI, p.TaqI, and p.FokI), and, HNF1A gene (encoding as SNPs p.I27L, p.A98V, and p.S487N) were chosen because these genetic variants have been reported to be associated with type 2 diabetes, as well as GDM risk [12, 14–20]. We also investigated the obesity-related FTO gene rs9939609 SNP because it is associated with both GDM and gestational body weight during pregnancy [10, 13, 20].…”

Section: Introductionmentioning

confidence: 99%

Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus

Beysel

Eyerci

Ulubay

et al. 2019

Diabetol Metab Syndr

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Introduction Pre-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 methods Women 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. Results The 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). Conclusion The 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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Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor‐1α gene and the relationship to β‐cell function during an OGTT in glucose‐tolerant women with and without previous gestational diabetes mellitus

Abstract: The Ala/Val polymorphism at codon98 of HNF-1alpha is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM.

Cited by 17 publications

References 40 publications

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus

Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus

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