<i><scp>FUT</scp>2</i> non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

Ihara, Kenji; Fukano, Chika; Ayabe, Tadayuki; Fukami, Maki; Ogata, Tsutomu; Kawamura, Tomoyuki; Urakami, Tatsuhiko; Kikuchi, Nobuyuki; Yokota, Ichiro; Takemoto, Kana; Mukai, Tokuo; Nishii, Aki; Kikuchi, Toru; Mori, Tetsuo; Shimura, Naoto; Sasaki, Goro; Kizu, Rika; Takubo, Noriyuki; Soneda, Shun; Fujisawa, Takao; Takaya, Ryuzo; Kizaki, Zenro; Kanzaki, Sho; Hanaki, Keiichi; Matsuura, Nobuo; Kasahara, Yoshihito; Kosaka, Kitaro; Takahashi, Tomohiro; Minamitani, Kanshi; Matsuo, Seiichiro; Mochizuki, Hidetaka; Kobayashi, Kenichi; Koike, Akemi; Horikawa, Reiko; Teno, Shinichi; Tsubouchi, Kohji; Mochizuki, Takahiro; Igarashi, Yasuhiro; Amemiya, Shin; Sugihara, Shigetaka; Diabetes, Adolescent

doi:10.1111/dme.13288

Cited by 14 publications

(15 citation statements)

References 16 publications

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“…While most studies have investigated a link between age at menopause and cardiovascular outcomes, reporting an increased risk of CVD associated with early onset of menopause, few studies have examined a possible association between age at menopause with risk of type 2 diabetes [ 3 ]. Cross-sectional studies examining the association between age at menopause and type 2 diabetes have yielded contradictory results, showing either no association or an increased prevalence of type 2 diabetes in women who experience early onset of menopause [ 5 – 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Also, because the outcome (type 2 diabetes incidence) was assessed prospectively, the subjective measure of age at natural menopause would probably lead to non-differential misclassification with respect to the outcome, and would therefore bias estimates toward the null. Furthermore, previous reports indicate that the validity and reproducibility of self-reported age at menopause is fairly good [ 3 , 45 ]. In addition, mean age at natural menopause in the current study is similar to the mean age at natural menopause reported by other studies in the Netherlands and United States [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although menopause is a universal phenomenon in women, timing of the final menstrual period differs greatly [ 1 , 2 ], and is considered a marker of ageing and cardiovascular health [ 2 ]. Women with early onset of menopause (<45 years) have an increased risk of cardiovascular disease (CVD) and overall mortality, whereas menopause onset at age 50–54 years is linked to a reduced risk of CVD and mortality [ 3 ]. The increased risk of CVD and mortality is believed to be due to the adverse effects of early onset of menopause on CVD risk factors, but the influence of age at menopause on levels of cardiovascular risk factors remains unclear [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Type 2 diabetes is a major risk factor for CVD, and it is unclear whether age at menopause is associated with risk of type 2 diabetes [ 3 , 4 ]. Data from cross-sectional studies examining the association between age at menopause and type 2 diabetes are contradictory, with a few studies reporting no association and some other reporting higher odds of having type 2 diabetes with early onset of menopause [ 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

et al. 2017

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Aims/hypothesis In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators. Methods We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40-44 years; normal, 45-55 years; and late menopause, >55 years [reference]). Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits. HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens.Results During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes. After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (ptrend <0.001). The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association. Conclusions/interpretation Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

et al. 2017

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“…In contrast to genetics, environmental etiologies have not been validated and thus do not currently contribute to subject stratification in T1D prevention trials. However, some examples of gene-environment interactions include the interactions of the microbiome with the Fut-2 nonsecretor gene polymorphism, which increases risk of T1D and is associated with faster progression of presymptomatic T1D [10][11][12] , and interactions of picornaviruses, which include enteroviruses, with polymorphisms of the innate immunity viral RNA receptor gene region IFIH1(MDA-5) [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Type 1 Diabetes: Disease Stratification

Insel¹,

Dutta²,

Hedrick³

2017

Biomed Hub

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Type 1 diabetes, a disorder characterized by immune-mediated loss of functional pancreatic beta cells, is a disease continuum with specific presymptomatic stages with defined risk of progression to symptomatic disease. Prognostic biomarkers have been developed for disease staging and for stratification of subjects that address the heterogeneity in rate of disease progression. Using biomarkers for stratification of subjects at different stages of type 1 diabetes will enable smaller and shorter intervention clinical trials with greater effect size. Addressing the heterogeneity of the disease will allow precision medicine-based approaches to prevention and interception of presymptomatic stages of disease and treatment and cure of symptomatic disease.

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Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank

et al. 2021

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The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease‐related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair‐wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups.

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FUT2 non‐secretor status is associated with Type 1 diabetes susceptibility in Japanese children

Abstract: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Cited by 14 publications

References 16 publications

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

Type 1 Diabetes: Disease Stratification

Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank

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