Calpain-10 (NIDDM1) as a Susceptibility Gene for Common Type 2 Diabetes

Horikawa, Yukio

doi:10.1507/endocrj.kr-70

Cited by 16 publications

(4 citation statements)

References 47 publications

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“…CAPN10 mRNA is expressed in various tissues in human body including pancreatic islets, muscle and liver, which are three most important tissues controlling glucose homeostasis. Thus, although its exact mechanism is not known, it is suggested that CAPN10 is involved in insulin secretion of pancreatic β-cells possibly by regulating exocytosis in pancreatic β-cells [ 5 6 16 ] as well as insulin action and hepatic glucose production [ 17 ]. Moreover, 14 calpain isoenzymes and their encoding genes have been identified up to now, and the CAPN10 gene among them is currently highlighted in terms of obesity and diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…However, other studies showed a single genotype to be associated with type 2 diabetes. A study conducted in British/Irish population reported that a single genotype in SNP-44 of CAPN10 was related to type 2 diabetes but not SNP-43, -19, and -63 [ 4 17 ]. Also, studies in Mexican and Indian populations showed diverse associations [ 21 22 ], suggesting an ethnic difference in the association between CAPN10 polymorphism and diabetes among different populations [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, plasma levels of adiponectin secreted in adipocytes were significantly higher in control group compared to diabetes group. Adiponectin increases insulin sensitivity by augmenting fatty acid oxidation in muscles and reducing gluconeogenesis in the liver [ 17 22 ]. These adiponectin effects are known to be attributed to activation of 5`adenosine monophosphate-activated protein activated protein kinase which is a key enzyme involved in fatty acid oxidation and glucose intake in muscles and gluconeogenesis in the liver [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients

et al. 2018

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BackgroundGenetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients.MethodsOverall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes.ResultsAmong calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion.ConclusionVariations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients

et al. 2018

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“…23 Moreover, it was postulated that ethnic differences may influence the association between CAPN10 and T2DM. 24 Although individuals with 1-1-2/1-2-1 diplotype were more frequent in PTDM group, we were unable to confirm an association between PTDM and that 'high T2DM risk diplotype', as evaluated in an European 25 possibly due to lower number of cases. However, postulated PTDM induction mechanism differs from that for T2DM, and includes additional risk factors, for example, the immunosuppressive regimen, 17 which may be also responsible for observed discrepancies.…”

Section: Discussionmentioning

confidence: 58%

Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus

Kurzawski

Dziewanowski²,

Kędzierska

et al. 2009

Pharmacogenomics J

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New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney transplant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G4A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C4T) using PCR-based assays. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P ¼ 0.056), and an association of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR) ¼ 2.45, P ¼ 0.023) was observed. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR ¼ 2.35, P ¼ 0.026). Patients' higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk factors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in relation to PTDM risk. However, the application of SNP-63 (rs5030952:C4T) as a marker of PTDM should be verified by further independent studies.

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