Takafumi Tsuchiya

Publications of Takafumi Tsuchiya

• Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome.

  Authors: Toshihide Kawai, Maggie C Y Ng, M Geoffrey Hayes, Issei Yoshiuchi, Takafumi Tsuchiya, Heather Robertson, Nancy J Cox, Kenneth S Polonsky, Graeme I Bell, David A Ehrmann

  Diabetes research and clinical practice. 09/2009;

  Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by chronic anovulation, hyperandrogenism, obesity and a predisposition to type 2 diabetesPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by chronic anovulation, hyperandrogenism, obesity and a predisposition to type 2 diabetes mellitus (T2DM). Since obesity plays an important role in the etiology of PCOS, we sought to determine if variants in the perilipin gene (PLIN), a gene previously implicated in the development of obesity, were also associated with PCOS. We typed six single nucleotide polymorphisms (haplotype tagging and/or previously associated with obesity or related metabolic traits) in PLIN in 305 unrelated non-Hispanic white women (185 with PCOS and 120 without PCOS). None of the variants was associated with PCOS (P<0.05). However, the variant rs1052700*A was associated with increased risk for glucose intolerance (impaired glucose tolerance or T2DM) in both non-PCOS (OR=1.75 [1.02-3.01], P=0.044) and PCOS subjects (OR=1.67 [1.08-2.59], P=0.022). It was also associated with increased LDL (P=0.007) and total cholesterol levels (P=0.042). These results suggest that genetic variation in PLIN may affect glucose and lipid metabolism in women both with and without PCOS.

• Patterns of linkage disequilibrium in the type 2 diabetes gene calpain-10.

  Authors: M Geoffrey Hayes, Laura Del Bosque-Plata, Takafumi Tsuchiya, Craig L Hanis, Graeme I Bell, Nancy J Cox

  Diabetes. 01/2006; 54(12):3573-6.

  We investigated the patterns and extent of linkage disequilibrium (LD) in the vicinity of the type 2 diabetes gene calapin-10 (CAPN10) in Mexican Americans, European Americans, African Americans, andWe investigated the patterns and extent of linkage disequilibrium (LD) in the vicinity of the type 2 diabetes gene calapin-10 (CAPN10) in Mexican Americans, European Americans, African Americans, and Chinese Americans. We found that CAPN10 occurs within a single block of high LD and that LD decays rapidly outside of the gene. This reduces the likelihood that associations between CAPN10 polymorphisms and type 2 diabetes could be attributed to variation at some distance from CAPN10. We also consistently observed that cases have more extensive LD than control subjects and that cases from families with evidence for linkage have more extensive LD than cases from families without evidence for linkage. These observations further suggest that there are one or more relatively common alleles increasing risk of type 2 diabetes in this local region.

• Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population.

  Authors: Naoko Iwasaki, Yukio Horikawa, Takafumi Tsuchiya, Yutaka Kitamura, Takahiro Nakamura, Yukio Tanizawa, Yoshitomo Oka, Kazuo Hara, Takashi Kadowaki, Takuya Awata [......] Naohisa Oda, Li Yu, Norihiro Yamada, Makiko Ogata, Naoyuki Kamatani, Yasuhiko Iwamoto, Laura Del Bosque-Plata, M Geoffrey Hayes, Nancy J Cox, Graeme I Bell

  Journal of human genetics. 01/2005; 50(2):92-8.

  Variation in the gene encoding the cysteine protease calpain-10 has been linked and associated with risk of type 2 diabetes. We have examined the effect of three polymorphisms in the calpain-10 geneVariation in the gene encoding the cysteine protease calpain-10 has been linked and associated with risk of type 2 diabetes. We have examined the effect of three polymorphisms in the calpain-10 gene (SNP-43, Indel-19, and SNP-63) on the development of type 2 diabetes in the Japanese population in a pooled analysis of 927 patients and 929 controls. We observed that SNP-43, Indel-19, and SNP-63 either individually or as a haplotype were not associated with altered risk of type 2 diabetes with the exception of the rare 111/221 haplogenotype (odds ratio (OR) =3.53, P=0.02). However, stratification based on the median age-at-diagnosis in the pooled study population (<50 and > or =50 years) revealed that allele 2 of Indel-19 and the 121 haplotype were associated with reduced risk in patients with later age-at-diagnosis (age-at-diagnosis > or =50 years OR=0.82 and 0.80, respectively; P=0.04 and 0.02). Thus, variation in the calpain-10 gene may affect risk of type 2 diabetes in Japanese, especially in older individuals.

• Linkage of calpain 10 to type 2 diabetes: the biological rationale.

  Authors: Nancy J Cox, M Geoffrey Hayes, Cheryl A Roe, Takafumi Tsuchiya, Graeme I Bell

  Diabetes. 03/2004; 53 Suppl 1:S19-25.

  The follow-up studies to the original report of association of variation at calpain 10 (CAPN10) with type 2 diabetes in the Mexican-American population of Starr County, Texas, encompass a broad rangeThe follow-up studies to the original report of association of variation at calpain 10 (CAPN10) with type 2 diabetes in the Mexican-American population of Starr County, Texas, encompass a broad range of science. There are association studies on genetic variation at CAPN10 in different human populations over a range of phenotypes related to type 2 diabetes, physiological studies on the biological functions of calpain proteases, and evolutionary studies on CAPN10 and the NIDDM1 region. We review here the studies published to date on CAPN10, as well as the latest findings from positional cloning studies on a number of other complex disorders. Collectively, these studies provide perspective on the challenges of moving from the linkage mapping and positional cloning studies on which we have been focused to an understanding of the biology shaping the relationship of genotype to phenotype at loci influencing susceptibility to complex disorders like type 2 diabetes.

• Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population.

  Authors: Laura Del Bosque-Plata, Carlos A Aguilar-Salinas, María Teresa Tusié-Luna, Salvador Ramírez-Jiménez, Maribel Rodríguez-Torres, Moisés Aurón-Gómez, Erika Ramírez, María Luisa Velasco-Pérez, Alfredo Ramírez-Silva, Francisco Gómez-Pérez, Craig L Hanis, Takafumi Tsuchiya, Issei Yoshiuchi, Nancy J Cox, Graeme I Bell

  Molecular genetics and metabolism. 03/2004; 81(2):122-6.

  Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10 gene (SNP-43, -43, -63, and -110 and Indel-19) to test for association with type 2 diabetes in 248 individuals representative of the mestizo population of Mexico City and Orizaba, Mexico including 134 patients with type 2 diabetes and 114 subjects with normal fasting blood glucose levels. We found a significant difference in SNP-44 allele and genotype frequencies between type 2 diabetic and non-diabetic subjects. The rare allele at SNP-44 was associated with increased risk of type 2 diabetes (odds ratio (OR)=2.72, 95% confidence interval (CI)=1.16-6.35, P=0.017). SNP-110, which is in perfect linkage disequilibrium with SNP-44, was also associated with type 2 diabetes. The SNP-43, Indel-19, and SNP-63 haplogenotype 112/121 associated with significantly increased risk (OR=2.16, 95% CI=1.31-3.57) of type 2 diabetes in Mexican Americans was not associated with significantly increased in risk in Mexicans (OR=1.15, 95% CI=0.57-2.34). The results suggest that variation in CAPN10 affects risk of type 2 diabetes in the mestizo population of central Mexico (Mexico City and Orizaba) and in Mexican Americans (Starr County, Texas).

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• Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family.

  Authors: Brian N Cockburn, Giovanna Bermano, Laura-Lee G Boodram, Surujpal Teelucksingh, Takafumi Tsuchiya, Deepak Mahabir, Andrew B Allan, Roland Stein, Kevin Docherty, Graeme I Bell

  The Journal of clinical endocrinology and metabolism. 02/2004; 89(2):971-8.

  This study investigated the prevalence of insulin promoter factor-1(IPF-1) mutations in familial early-onset diabetes mellitus in Trinidad. We screened 264 unrelated subjects with type 2 diabetesThis study investigated the prevalence of insulin promoter factor-1(IPF-1) mutations in familial early-onset diabetes mellitus in Trinidad. We screened 264 unrelated subjects with type 2 diabetes diagnosed before 40 yr of age and a family history of diabetes for mutations in the minimal promoter and coding region of the IPF-1 gene (IPF1). This study population included 169 patients of East Indian descent (Indo-Trinidadians), 66 of African descent (Afro-Trinidadians), and 29 of mixed ancestry. We identified five IPF1 variants, including one new missense mutation E224K, the previously described diabetes-associated duplication P242 P243dupP, two silent mutations in the codons for Leu54 (c.162G>A) and Ala256 (c.768C>A), and a substitution in the 5'-untranslated region (c.-18C>T). The E224K mutation was found in two unrelated diabetic Indo-Trinidadians and 0 of 60 controls. It was present on the same haplotype in both patients suggesting a founder effect. The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes. Functional studies of E224K showed reduced transactivation activity. IPF1 mutations leading to synthesis of a mutant protein may contribute to the development of familial early-onset diabetes/maturity-onset diabetes of the young in Indo-Trinidadians.

• Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population

  Authors: Laura del Bosque-Plata, Carlos A Aguilar-Salinas, Marı́a Teresa Tusié-Luna, Salvador Ramı́rez-Jiménez, Maribel Rodrı́guez-Torres, Moisés Aurón-Gómez, Erika Ramı́rez, Marı́a Luisa Velasco-Pérez, Alfredo Ramı́rez-Silva, Francisco Gómez-Pérez, Craig L Hanis, Takafumi Tsuchiya, Issei Yoshiuchi, Nancy J Cox, Graeme I Bell

  Molecular Genetics and Metabolism.

  Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10 gene (SNP-43, -43, -63, and -110 and Indel-19) to test for association with type 2 diabetes in 248 individuals representative of the mestizo population of Mexico City and Orizaba, Mexico including 134 patients with type 2 diabetes and 114 subjects with normal fasting blood glucose levels. We found a significant difference in SNP-44 allele and genotype frequencies between type 2 diabetic and non-diabetic subjects. The rare allele at SNP-44 was associated with increased risk of type 2 diabetes (odds ratio (OR)=2.72, 95% confidence interval (CI)=1.16–6.35, P=0.017). SNP-110, which is in perfect linkage disequilibrium with SNP-44, was also associated with type 2 diabetes. The SNP-43, Indel-19, and SNP-63 haplogenotype 112/121 associated with significantly increased risk (OR=2.16, 95% CI=1.31–3.57) of type 2 diabetes in Mexican Americans was not associated with significantly increased in risk in Mexicans (OR=1.15, 95% CI=0.57–2.34). The results suggest that variation in CAPN10 affects risk of type 2 diabetes in the mestizo population of central Mexico (Mexico City and Orizaba) and in Mexican Americans (Starr County, Texas).

• Association of the calpain-10 gene with type 2 diabetes in Europeans: Results of pooled and meta-analyses

  Authors: Takafumi Tsuchiya, Peter E.H. Schwarz, Laura del Bosque-Plata, M. Geoffrey Hayes, Christian Dina, Philippe Froguel, G. Wayne Towers, Sabine Fischer, Theodora Temelkova-Kurktschiev, Hannes Rietzsch [......] Marju Orho-Melander, Leif Groop, Maciej T. Malecki, Torben Hansen, Oluf Pedersen, Tasha E. Fingerlin, Michael Boehnke, Craig L. Hanis, Nancy J. Cox, Graeme I. Bell

  Molecular Genetics and Metabolism.

  We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR) = 1.11 (95% confidence interval (CI), 1.02–1.20), P = 0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR = 1.20 (1.03–1.41), P = 0.02; and 1-1-2/1-2-1, OR = 1.26 (1.01–1.59), P = 0.04) and one with decreased risk (1-1-1/2-2-1, OR = 0.86 (0.75–0.99), P = 0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR = 1.25 (1.05–1.50), P = 0.01). However, there was evidence for heterogeneity with respect to this effect (P = 0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P = 0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR = 1.19 (1.07–1.32), P = 0.001; 1-2-1/1-2-1 haplogenotype, OR = 1.46 (1.19–1.78), P = 0.0003; 1-1-2/1-2-1 haplogenotype, OR = 1.52 (1.12–2.06), P = 0.007; and 1-1-1/2-2-1 haplogenotype, OR = 0.83 (0.70–0.99), P = 0.03) and the meta-analysis (SNP-43*G, OR = 1.18 (1.05–1.32), P = 0.005; 1-2-1/1-2-1 haplogenotype, OR = 1.68 (1.33–2.11), P = 0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.

• Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses.

  Authors: Takafumi Tsuchiya, Peter E H Schwarz, Laura Del Bosque-Plata, M Geoffrey Hayes, Christian Dina, Philippe Froguel, G Wayne Towers, Sabine Fischer, Theodora Temelkova-Kurktschiev, Hannes Rietzsch [......] Marju Orho-Melander, Leif Groop, Maciej T Malecki, Torben Hansen, Oluf Pedersen, Tasha E Fingerlin, Michael Boehnke, Craig L Hanis, Nancy J Cox, Graeme I Bell

  Molecular genetics and metabolism. 89(1-2):174-84.

  We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.