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

Pihlajamäki, Jussi; Salmenniemi, Urpu; Vänttinen, Markku; Ruotsalainen, Eija; Vauhkonen, Ilkka; Kainulainen, Sakari; Ng, Maggie; Cox, Nancy J.; Bell, Graeme I.; Laakso, Markku

doi:10.1007/s00125-006-0270-z

Cited by 20 publications

(12 citation statements)

References 38 publications

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“…Most previous studies on Calpain-10 did not find a genderspecific effect of this gene on metabolic parameters. On the other hand, a previous study including offspring of patients with T2DM showed that SNP-43, but not SNP-19 or -44, was associated with the intra-abdominal fat area in men and the authors suggested that Calpain-10 may increase the risk of T2DM via affecting abdominal obesity in men with high risk for T2DM [31]. Therefore, the relationship between Calpain-10 and increased BMI in men presented in our study needs to be investigated extensively.…”

Section: Prace Oryginalnementioning

confidence: 96%

Wpływ polimorfizmu genu kalpainy-10 na rozwój cukrzycy typu 2 w populacji tureckiej

Arslan¹,

Açık²,

Gunaltili³

et al. 2014

Endokrynologia Polska

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Introduction: The variations in the Calpain-10 gene have been suggested to be related to susceptibility to type 2 diabetes mellitus (T2DM) in different populations. In this study, we investigated the relationship between single nucleotide polymorphism (SNP)-19, -44 and -63 in the Calpain-10 gene and the development of T2DM in a Turkish population. Material and methods: A total of 211 subjects were recruited: 118 patients with a diagnosis of T2DM and 93 unrelated healthy subjects. Results: There were no significant differences in the genotype and allele distribution of SNPs studied between the patients with T2DM and controls (p > 0.05), whereas the frequencies of 121 haplotype and 122/121 haplotype combination were found to be higher in patients with T2DM than in controls (p < 0.05). No association was observed between the variations in the Calpain-10 gene and glycaemic control and lipid parameters (p > 0.05). The SNP-19 insertion/insertion was significantly related to increased body mass index (BMI) in male diabetic patients (p < 0.05).

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Section: Prace Oryginalnementioning

confidence: 96%

Wpływ polimorfizmu genu kalpainy-10 na rozwój cukrzycy typu 2 w populacji tureckiej

Arslan¹,

Açık²,

Gunaltili³

et al. 2014

Endokrynologia Polska

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“…Similar to other calpains, CAPN10 consists of an isoform-specific large subunit and a common small subunit, and was shown to function as intracellular calcium-dependent cysteine proteases in calcium-regulated signaling pathways [5]. CAPN10 is expressed at the mRNA and protein levels by several tissue types, with different mRNA isoforms reported, in particular those involved in the regulation of glucose homeostasis, such as pancreatic β islet cells, liver, skeletal muscle, and adipocytes [6,7]. …”

Section: Introductionmentioning

confidence: 99%

“…Several case control and association studies indicated that polymorphisms in CAPN10 are associated with the development of T2D and insulin resistance, more so in obese patients with an earlier age of disease onset [6,8-10]. These include the at-risk UCSNP-43 G/A variant located in the third intron, UCSNP-19 2R (two 32-bp repeats)/3R (three 32-bp repeats) present in intron 6, and UCSNP-63 C/T variant within CAPN10 intron 13 [7,10]. This contribution of the CAPN10 variants to T2D pathogenesis was highlighted by the findings that select UCSNP-43/UCSNP-19/UCSNP -63 haplotypes (112 and 121) were associated with heightened risk of T2D in select ethnic groups, and as at-risk dipolotypes (haplotype combinations) were reported for many populations [10-13].…”

Section: Introductionmentioning

confidence: 99%

Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study

et al. 2010

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BackgroundGenetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D).MethodsWe examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsEnrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls.ConclusionsCAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.

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“…Second, we investigated ten polymorphisms in nine genes (ADRB1, ADRB2, ADRB3, CAPN10, IRS1, UCP2, PPARGC1A, PTPN1 and ENPP1), each of which has been associated with at least two components contributing to the metabolic syndrome [19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

The search for putative unifying genetic factors for components of the metabolic syndrome

et al. 2008

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Aims/hypothesis The metabolic syndrome is a cluster of factors contributing to increased risk of cardiovascular disease and type 2 diabetes but unifying mechanisms have not been identified. Our aim was to study whether common variations in 17 genes previously associated with type 2 diabetes or components of the metabolic syndrome and variants in nine genes with inconsistent association with at least two components of the metabolic syndrome would also predict future development of components of the metabolic syndrome, individually or in combination. Methods Genetic variants were studied in a large prospective study of 16,143 non-diabetic individuals (mean followup time 23 years) from the Malmö Preventive Project. In this study, development of at least three of obesity (BMI≥ 30 kg/m 2 ), dyslipidaemia (triacylglycerol≥1.7 mmol/l and/ or lipid-lowering treatment), hypertension (blood pressure≥ 140/90 mmHg and/or antihypertensive medication) and hyperglycaemia (fasting plasma glucose≥5.6 mmol/l and/or known diabetes) was defined as development of the metabolic syndrome. The risk of developing at least three components of the metabolic syndrome or the individual components was calculated by logistic regression adjusted for age at baseline, follow-up time and sex. Results Polymorphisms in TCF7L2 (rs7903146, OR 1.10, 95% CI 1.04-1.17, p=0.00097), FTO (rs9939609, OR 1.08, 95% CI 1.02-1.14, p=0.0065), WFS1 (rs10010131, OR 1.07, 95% CI 1.02-1.13, p=0.0078) and IGF2BP2 (rs4402960, OR 1.07, 95% CI 1.01-1.13, p = 0.021) predicted the development of at least three components of the metabolic syndrome in both univariate and multivariate analysis; in the case of TCF7L2, WFS1 and IGF2BP this was due to their association with hyperglycaemia (p< 0.00001, p=0.0033 and p=0.027, respectively) and for FTO it was due to its association with obesity (p=0.004). A polymorphism in the GCKR gene predicted dyslipidaemia (rs1260326, OR 1.15, 95% CI 1.09-1.22, p<0.00001) but not the metabolic syndrome. None of the studied polymorphisms was associated with more than two components of the metabolic syndrome. A composite genotype score of the 17 polymorphisms associated with type 2 diabetes predicted the development of at least three components of the metabolic syndrome (OR 1.04, p<0.00001) and the development of hyperglycaemia (OR 1.06, p<0.00001).Carriers of ≥19 risk alleles had 51 and 72% increased risk of developing at least three components of the metabolic syndrome and hyperglycaemia, respectively, compared with carriers of ≤12 risk alleles (p<0.00001 for both). Conclusions/interpretation Polymorphisms in susceptibility genes for type 2 diabetes (TCF7L2, WFS1, IGF2BP2) and obesity (FTO) predispose to the metabolic syndrome by Diabetologia

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

Cited by 20 publications

References 38 publications

Wpływ polimorfizmu genu kalpainy-10 na rozwój cukrzycy typu 2 w populacji tureckiej

Wpływ polimorfizmu genu kalpainy-10 na rozwój cukrzycy typu 2 w populacji tureckiej

Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study

The search for putative unifying genetic factors for components of the metabolic syndrome

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