A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance

Baier, Leslie J.; Permana, Paskasari A.; Yang, Xiaolin; Pratley, Richard E.; Hanson, Robert L.; Shen, Gong-Qing; Mott, David M.; Knowler, William C.; Cox, Nancy J.; Horikawa, Yukio; Oda, Naohisa; Bell, Graeme I.; Bogardus, Clifton

doi:10.1172/jci10665

Cited by 269 publications

(238 citation statements)

References 13 publications

Supporting

Mentioning

219

Contrasting

Unclassified

Order By: Relevance

“…The GG genotype of SNP-43 has been associated with type 2 diabetes and insulin resistance [4,27], whereas in this study the A allele, and a haplotype carrying this allele, was associated with intra-abdominal obesity. These apparently discrepant findings may be due to the fact that the effects of calpain-10 on clinical measures may be complex and difficult to investigate in cross-sectional studies, similar to the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 gene [33][34][35][36].…”

Section: Subjects Incontrasting

confidence: 55%

“…Thr504Ala) or may affect the levels of expression of calpain-10, e.g. SNP-43 in fat and skeletal muscle [2,4,28,29]. The novel finding of the present study was that SNP-43 affects intra-abdominal obesity and insulin sensitivity in offspring of patients with type 2 diabetes (Study I).…”

Section: Subjects Inmentioning

confidence: 56%

“…However, other studies have not found an association of the G allele with type 2 diabetes or insulin resistance [6][7][8], and other SNPs and/or haplotypes in the same locus have been proposed to be more important for glucose metabolism [6,[9][10][11]. The mechanisms by which the G allele of SNP-43 leads to lower rates of glucose disposal and higher rates of lipid oxidation [4] are unknown, but have been proposed to be related to high levels of NEFA [12]. Alternatively, polymorphisms in this locus could regulate energy expenditure [4], thermogenesis [13] and insulin secretion [14].…”

Section: Introductionmentioning

confidence: 99%

“…Calpain-10 is a calcium-activated protein expressed in all human tissues [3], but the biochemical and physiological mechanism(s) by which it affects the risk of type 2 diabetes remain unclear. The G allele of the single nucleotide polymorphism (SNP)-43, has been associated with insulin resistance [4] and type 2 diabetes in both cross-sectional [2] and prospective studies [5]. However, other studies have not found an association of the G allele with type 2 diabetes or insulin resistance [6][7][8], and other SNPs and/or haplotypes in the same locus have been proposed to be more important for glucose metabolism [6,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms by which the G allele of SNP-43 leads to lower rates of glucose disposal and higher rates of lipid oxidation [4] are unknown, but have been proposed to be related to high levels of NEFA [12]. Alternatively, polymorphisms in this locus could regulate energy expenditure [4], thermogenesis [13] and insulin secretion [14].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: The mechanisms by which the calpain-10 gene (CAPN10) affects the risk of type 2 diabetes are unclear. Therefore, we investigated the effects of four polymorphisms in CAPN10 (single nucleotide polymorphism [SNP]-43, SNP-44, Insertion/Deletion [Indel]-19 and SNP-63) on insulin secretion, insulin action and abdominal fat distribution in offspring of patients with type 2 diabetes. Subjects and methods: Insulin secretion was determined by an IVGTT, insulin action by the hyperinsulinaemic-euglycaemic clamp and abdominal fat distribution by computed tomography in 158 non-diabetic offspring (age 34.9±6.3 years [mean±SD], BMI 26.2± 4.9 kg/m 2 ) of type 2 diabetic patients. Results: SNP-43 (p=0.009 over the three genotypes, adjusted for age, sex, BMI and family relationship) and haplotypes carrying the A allele of SNP-43 were associated with intra-abdominal fat area. The A allele of SNP-43 was associated with intraabdominal fat area in men (p=0.014) but not in women. were not associated with intra-abdominal fat area or insulin action. Furthermore, we demonstrated in a separate sample of middle-aged men (n=234) who had a history of type 2 diabetes in firstdegree relatives that the A allele of SNP-43 was associated with a large waist circumference, and high insulin levels in an OGTT.Conclusions/interpretation: SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.

show abstract

Section: Subjects Incontrasting

confidence: 55%

Section: Subjects Inmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

et al. 2006

View full text Add to dashboard Cite

show abstract

Genome Scans of Type 2 Diabetes Mellitus

Rutherford

Shuldiner

Mitchell

2003

International Textbook of Diabetes Mellitus

View full text Add to dashboard Cite

Type 2 diabetes mellitus affects approximately 5–8% of the industrial world. Although a genetic basis to the disease is widely accepted, identification of the specific mutations involved is difficult because of the heterogeneous and multifactorial nature of the disease. With the availability of large‐scale genotyping techniques, genome‐wide linkage approaches are now commonly used to localize regions along the chromosome likely to harbor diabetes susceptibility genes. This chapter presents an overview of the genome scan approach and a summary of linkage results reported from a variety of populations.

show abstract

Molecular Genetics of Type 2 Diabetes—Candidate Genes

Groop

Ridderstråle

2004

International Textbook of Diabetes Mellitus

View full text Add to dashboard Cite

About 150 million people are diagnosed with type 2 diabetes today and it is predicted that this number will double within the next 15 years. There is evidence that type 2 diabetes is inherited; however, it is unlikely that the cause of the explosion of type 2 diabetes is found in our genes. It is rather the rapid change of the environment with an affluent westernized society that triggers the epidemic in genetically predisposed individuals. In this chapter we discuss potential candidate genes that could contribute to this genetic predisposition to type 2 diabetes.

show abstract

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance

Cited by 269 publications

References 13 publications

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

Genome Scans of Type 2 Diabetes Mellitus

Molecular Genetics of Type 2 Diabetes—Candidate Genes

Contact Info

Product

Resources

About