Akane Ide

Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset

This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to or clinical presentation of type 1 diabetes. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 128 Japanese patients with type 1 diabetes and in 107 healthy control subjects in a case-controlled study. The allelic and haplotypic frequencies of the IL-10 gene promoter region polymorphisms were similar in patients with type 1 diabetes and in control subjects. However, the -819T and -592A allele were associated with adult-onset (>18 years) of the disease (p = 0.037). Furthermore, the frequency of ATA haplotype was increased in adult-onset patients than that in early-onset patients (< or =18 years; p = 0.037). Among the genotypes comprising ATA haplotype, the frequency of ATA/ATA was significantly higher in adult-onset patients than in early-onset patients (p = 0.004). These results suggest that the IL-10 gene promoter polymorphisms are associated with the age-at-onset in Japanese patients with type 1 diabetes.

Correlation between interleukin 10 gene promoter region polymorphisms and clinical manifestations in Japanese patients with Sjögren’s syndrome

Sjogren’s syndrome (SS) is an autoimmune disease characterised by lymphocytic infiltration and glandular tissue dysfunction of exocrine glands such as the salivary and lachrymal glands in genetically susceptible people. Several cytokines, including interleukin 10 (IL10), have been proposed to have a role in the pathogenesis of the disease. Although the major genes involved in susceptibility to SS are within the major histocompatibility complex (MHC) region, several putative non-MHC genetic loci (Ro52,1 IL1,2 IL6,3 Fas/FasL,4 mannose binding lectin,5,6 TAP2,7 and glutathione S-transferase M1 gene8 ) have been proposed as candidate genes. Recently, Hulkkonen et al reported that in Finnish patients the haplotypes formed on the basis of the IL10 gene alleles (at the -1082, -819, and -592 loci) were related to susceptibility to primary SS.9 However, no correlation between extraglandular symptoms …

Association of Interleukin-18 Gene Promoter Polymorphisms in Type 1 Diabetes and Autoimmune Thyroid Disease

Abstract: Type 1 diabetes is a heterogeneous autoimmune disease and is often associated with other organ‐specific autoimmune diseases, including autoimmune thyroid disease (AITD). IL‐18 is a potent proinflammatory cytokine capable of inducing IFN‐γ production that is associated with the development of type 1 diabetes and AITD. The gene for IL‐18 is located near Idd2 and has been reported to be associated with a susceptibility to type 1 diabetes. To test the putative involvement of IL‐18 gene polymorphism in predisposition to type 1 diabetes and AITD, we conducted a case‐control study in Japanese population. The SNPs at position −607 (C/A) and −137 (G/C) in the promoter region of the IL‐18 gene were analyzed by sequence‐specific PCR in 74 nondiabetic patients with AITD, 47 type 1 diabetic patients with AITD, and 114 normal controls. There was no significant increase in the genotype and allele frequencies not only in nondiabetic patients with AITD compared with normal controls, but also in type 1 diabetic patients with AITD compared with normal controls. The distribution of IL‐18 gene haplotypes was also similar between both patient groups and normal controls. These results suggest that polymorphisms of the IL‐18 gene are not associated with a susceptibility to AITD and type 1 diabetes coexistent with AITD in Japanese population.

Elevation of Serum Pro-Gastrin - Releasing Peptide in Patients with Medullary Thyroid Carcinoma and Small Cell Lung Carcinoma

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.

Stromal Cell-Derived Factor-1 Chemokine Gene Variant in Patients with Type 1 Diabetes and Autoimmune Thyroid Disease

Abstract: Type 1 diabetes is a heterogenous autoimmune disease and is frequently associated with other organ‐specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to have clinical and immunological features distinct from patients without AITD. This study investigated whether stromal cell‐derived factor (SDF)‐1 gene polymorphism is associated with susceptibility to type 1 diabetes and AITD. SDF‐1 is a powerful chemokine that upregulates T‐cell migration and activation, and the gene for SDF‐1 is located near type 1 diabetes susceptibility locus IDDM10. The SDF1‐3′A variant (801 G to A in the 3′‐untranslated region) was determined by the PCR‐RFLP technique in 54 type 1 diabetic patients with AITD, 75 type 1 diabetic patients without AITD, 137 nondiabetic patients with AITD, and 106 healthy subjects in a case‐control study. No significant differences on the allele and genotype frequencies of the SDF1 gene polymorphism were found, not only in type 1 diabetic patients with AITD compared with normal controls but also between nondiabetic patients with AITD and healthy control subjects. These results suggest that the SDF1‐3′A variant is not associated with genetic susceptibility to type 1 diabetic patients and AITD.

Epitope Analysis of GAD65 Autoantibodies in Japanese Patients with Autoimmune Diabetes

Abstract: Type 1 diabetes is an organ‐specific autoimmune disease characterized by T cell‐mediated destruction of pancreatic β cells. In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA‐2 are the important immunological features of type 1 diabetes. The prevalences of anti‐islet autoantibodies in patients with Japanese type 1 diabetes are 60‐70% for GAD autoantibodies, 45‐50% for insulin autoantibodies (IAA), and 60‐65% for IA‐2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosis‐prone, there are a number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset called LADA. These patients with LADA often progress toward an insulin‐deficient state within several years after diagnosis. High levels of GAD autoantibodies have a high predictive value for future insulin deficiency in LADA. Further, epitope analysis of GAD65 autoantibodies may be helpful to predict future insulin dependency in LADA patients. In conclusion, Japanese patients with type 1 diabetes are clinically heterogeneous and the determination of immunological features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.

Interleukin-10 Gene Promoter Region Polymorphisms in Patients with Type 1 Diabetes and Autoimmune Thyroid Disease

Abstract: Type 1 diabetes is a heterogeneous autoimmune disease and is frequently associated with other organ‐specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to show distinct clinical and immunological features from patients without AITD. This study investigated whether interleukin‐10 (IL‐10) gene promoter region polymorphisms are associated with susceptibility to type 1 diabetes and AITD. The frequency of −1082G/A, −819C/T, and −592C/A polymorphisms was analyzed in 54 type 1 diabetic patients with AITD, 74 type 1 diabetic patients without AITD, 124 nondiabetic patients with AITD, and 107 healthy subjects in a case‐control study. No significant differences on the allele and genotype frequencies of three polymorphisms were found not only in type 1 diabetic patients with AITD compared with normal controls, but also between nondiabetic patients with AITD and healthy controls. The distribution of IL‐10 gene haplotypes was also similar between both patient groups and normal controls. These results suggest that IL‐10 gene promoter region polymorphisms are not associated with genetic susceptibility to type 1 diabetes and AITD.

Maternal thyroid function and child IQ

We read with great interest the Article by Tim Korevaar and colleagues showing that both high and low maternal free thyroxine in early pregnancy are associated with a signifi cant decrease in child intelligence quotient (IQ). We previously reported that thyroid function in early pregnancy in Japanese women, who generally have suffi cient iodine intake, had no relevance to parameters in neonates, scores of fetal maturation, or child development. Free thyroxine increase in early pregnancy is a physiologically adaptive change induced by circulating asialo-human chorionic gonadotropin and is associated with severity of morning sickness. Typical cases are characterised by gestational thyrotoxicosis and usually accompanied by hyperemesis gravidarum. Increased free thyroxine is often complicated by maternal malnutrition. Early fetal brain development might be aff ected by maternal nutrition and thus decreased IQ should also be assessed in relation to the possible presence of maternal nutritional disorders.

Contents Vol. 5, 2016

Maria Alevizaki – Athens University, Athens, Greece Ana Aranda – Universidad Autónoma de Madrid, Madrid, Spain Rebecca Bahn – Mayo Medical School, Rochester, Minn., USA Paul Banga – King’s College London School of Medicine, London, UK Luigi Bartalena – University of Insubria, Varese, Italy Bernadette Biondi – University of Naples Federico II, Naples, Italy Anita Boelen – Academic Medical Center, Amsterdam, Netherlands Georg Brabant – University of Lübeck, Lübeck, Germany Henning Dralle – Martin Luther University, Halle/Saale, Germany Creswell J. Eastman – The University of Sydney, Westmead, N.S.W., Australia Murat Erdogan – Ibni-i-Sina Hastanesi, Ankara, Turkey Valentin Fadeyev – Federal Endocrinological Scientific Centre, Moscow, Russia Ulla Feldt-Rasmussen – Copenhagen Univ. Hosp., Rigshospitalet, Copenhagen, Denmark Laszlo Hegedus – Odense University Hospital, Odense, Denmark George J. Kahaly – Gutenberg University Medical Center, Mainz, Germany Rui Maciel – Universidade Federal de São Paulo, São Paulo, Brazil Ana Luiza Maia – Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Jens Mittag – University of Lübeck, Lübeck, Germany Ralf Paschke – Universität Leipzig, Leipzig, Germany Robin P. Peeters – Erasmus MC, Rotterdam, Netherlands