Eri Ejima

Clinical and Genetic Characteristics of Autoimmune Polyglandular Syndrome Type 3 Variant in the Japanese Population

OBJECTIVE Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid disease (AITD), and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population. DESIGN/PATIENTS Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present. RESULTS A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects. CONCLUSIONS In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms.

Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism

Objective  A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic‐bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors.

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.

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.