Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.
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PMID:Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. 1189 Oct 23

Recently, a positional cloning study proposed that haplotypes at the calpain-10 locus (CAPN10) are associated with increased risk of type 2 diabetes, or non-insulin-dependent diabetes mellitus, in Mexican Americans, Finns, and Germans. To inform the interpretation of the original mapping results and to look for evidence for the action of natural selection on CAPN10, we undertook a population-based genotyping survey of the candidate susceptibility variants. First, we genotyped sites 43, 19, and 63 (the haplotype-defining variants previously proposed) and four closely linked SNPs, in 561 individuals from 11 populations from five continents, and we examined the linkage disequilibrium among them. We then examined the ancestral state of these sites by sequencing orthologous portions of CAPN10 in chimpanzee and orangutan (the identity of sites 43 and 19 was further investigated in a limited sample of other great apes and Old World and New World monkeys). Our survey suggests larger-than-expected differences in the distribution of CAPN10 susceptibility variants between African and non-African populations, with common, derived haplotypes in European and Asian samples (including one of two proposed risk haplotypes) being rare or absent in African samples. These results suggest a history of positive natural selection at the locus, resulting in significant geographic differences in polymorphism frequencies. The relationship of these differences to disease risk is discussed.
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PMID:Geographic and haplotype structure of candidate type 2 diabetes susceptibility variants at the calpain-10 locus. 1189 18

Polycystic ovary syndrome (PCOS) is associated with an increased risk of impaired glucose tolerance and type 2 diabetes. Recent evidence suggests that variation in the gene encoding the cysteine protease calpain-10 influences susceptibility to type 2 diabetes. The present study was undertaken to determine whether variation in this gene is associated with quantitative traits pertinent to the pathogenesis of PCOS and diabetes. We studied 212 women with PCOS (124 white of European ancestry, 57 African-American, 13 Hispanic, 13 Asian-American, and 5 Middle-Eastern). Each subject was genotyped for 3 DNA polymorphisms in the calpain-10 gene associated with type 2 diabetes (SNP-43, -19, and -63). The white and African-American subjects were examined for association of these polymorphisms with phenotypic features of PCOS and type 2 diabetes. There were not enough individuals in the other groups for similar genotype/phenotype analyses. Nineteen (9%) of the 212 women with PCOS were diabetic and were not included in the genotype/phenotype analyses. Twelve (63%) of these subjects were African-American. Phenotypic traits in nondiabetic white probands did not differ whether analyzed for each individual SNP (SNP-43, -19, -63) or haplotype combination. Nor was there association of SNP-43, -19, or -63 with any of the phenotypic features of type 2 diabetes or PCOS in nondiabetic African-Americans. However, nondiabetic African-Americans with the 112/121-haplotype combination had significantly higher insulin levels, in response to an oral glucose challenge, as reflected in the area under the insulin curve (257,021 +/- 95,384 vs. 136,240 +/- 11,468 pmol/min; P = 0.03), compared with those with other haplotypes. This finding was particularly notable because the 112/121 subjects were less obese. The difference between groups in area under the insulin response curve remained significant (P = 0.002 by analysis of covariance) after adjustment for body mass index. In addition to its association with insulin levels in African-Americans, the 112/121-haplotype combination was associated with an approximate 2-fold increase in risk of PCOS in both African-Americans and whites.
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PMID:Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome. 1193 99

Variations in the calpain-10 gene have recently been reported to be associated with type 2 diabetes in a Mexican-American population. We typed three single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNPs 43, 56, and 63) to test for association between variation at these loci and type 2 diabetes and diabetes-related traits in 1,603 Finnish subjects: two samples of 526 (Finland-U.S. Investigation of NIDDM Genetics [FUSION] 1) and 255 (FUSION 2) index case subjects with type 2 diabetes, 185 and 414 unaffected spouses and offspring of FUSION 1 index case subjects or their affected siblings, and 223 elderly normal glucose-tolerant control subjects. We found no significant differences in allele, genotype, haplotype, or haplogenotype frequencies between index case subjects with diabetes and the elderly and spouse control populations (all P > 0.087). Although variation in these three SNPs was associated with variation in some type 2 diabetes-related traits within each of the case and control groups, no consistent pattern of the implicated variant or combination of variants was discerned. We conclude that variation in these three SNPs in the calpain-10 gene is unlikely to confer susceptibility to type 2 diabetes in this Finnish cohort.
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PMID:Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. 1197 69

Variation within the calpain-10 gene (CAPN10) has been proposed to account for linkage to type 2 diabetes on chromosome 2q in Mexican-Americans, and associations with diabetes have been reported in several other populations. Given the epidemiological, physiological, and genetic overlap between type 2 diabetes and polycystic ovary syndrome (PCOS), CAPN10 represents a strong candidate gene for a role in PCOS susceptibility. Using both family based and case-control association resources (146 parent-offspring trios; 185 additional PCOS cases; 525 control subjects, all of European ancestry), we sought association between CAPN10 variation and PCOS, focusing on four single nucleotide polymorphism (SNP) variants (SNP-44, SNP-43; SNP-19; SNP-63). On single-locus transmission disequilibrium analysis in the 146 trios, there was nominal evidence (P = 0.03) of excess transmission of the more common allele at SNP-63. This association was not, however, replicated in the case-control analysis. No other significant associations were observed at the single-locus or haplotype level in either the transmission-disequilibrium or case-control analyses. The relative risk for the high-risk diabetes susceptibility 112/121 genotype (SNPs 43-19-63) was 0.84 (95% confidence intervals, 0.40-1.71). No associations were seen with intermediate traits of relevance to diabetes and PCOS pathogenesis. We have found no evidence from these analyses that CAPN10 gene variation influences susceptibility to PCOS.
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PMID:Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome. 1205 Feb 23

Polymorphism in the calpain-10 gene is linked to type 2 diabetes, insulin resistance, and decreased thermogenesis. In view of the role of beta-adrenoceptors in thermogenesis we investigated the relationship between beta(1)-, beta(2)-, and beta(3)-adrenoceptor-stimulated lipolysis in abdominal sc fat cells and 3 different previously described single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNP-19, SNP-43, and SNP-63). The study sample comprised 240 healthy subjects. A strong association between lipolytic beta(3)-receptor function in adipocytes and the SNP-19, which is a deletion/insertion (1/2) was observed in overweight subjects (body mass index, >25 kg/m(2)), but not in lean ones. No association was found between any of the polymorphisms and lipolytic function of either beta(1)- or beta(2)-receptors. Carriers of 1/1 in SNP-19 had 30-fold decreased lipolytic sensitivity of beta(3)-adrenoceptors in comparison to 1/2 or 2/2 carriers (P = 0.0019, by ANOVA). This was found in both genders and was not influenced by SNP-43 or SNP-63 in the calpain-10 gene or by the Trp(64)Arg polymorphism in the beta(3)-adrenoceptor gene. In conclusion, a deletion/insertion polymorphism in the calpain-10 gene (SNP-19) is associated with reduced beta(3)-adrenoceptor function in obesity. This could be of importance for regulating thermogenesis in overweight subjects.
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PMID:Calpain-10 gene polymorphism is associated with reduced beta(3)-adrenoceptor function in human fat cells. 1210 50

The calpain-10 gene (CAPN10) has been associated with type 2 diabetes, but information on molecular and physiological mechanisms explaining this association is limited. Here we addressed this question by studying the role of CAPN10 for phenotypes associated with type 2 diabetes and free fatty acid (FFA) metabolism. Among 395 type 2 diabetic patients and 298 nondiabetic control subjects from Finland, the SNP-43 allele 1 (P = 0.011), SNP-63 allele 2 (P = 0.010), and the haplotype combination SNP-44/43/19/63 1121/1121 (P = 0.028) were associated with type 2 diabetes. The SNP-43 genotypes 11 and 12 were associated with higher fasting insulin and homeostasis model assessment (HOMA) insulin resistance index among control subjects (P = 0.021 and P = 0.0076) and with elevated FFA among both control subjects (P = 0.0040) and type 2 diabetic patients (P = 0.0025). Multiple regression analysis further indicated that SNP-43 is an independent predictor of FFA levels (P = 0.0037). Among 80 genotype discordant sibling pairs, the SNP-43 allele 1 was associated with elevated fasting serum insulin and HOMA index (P = 0.013 and P = 0.0068). None of the four SNPs showed distorted transmission of alleles to patients with type 2 diabetes in a qualitative transmission disequilibrium test, including 108 trios. Because FFA and insulin resistance are known to predict type 2 diabetes, the finding that variation in the CAPN10 gene influences FFA levels and insulin resistance may provide an explanation for how the CAPN10 gene increases susceptibility to type 2 diabetes.
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PMID:Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. 1214 85

Both type 2 diabetes mellitus (T2DM) and insulin resistance are complex traits in which multiple gene effects and metabolic and environmental factors combine to contribute to the overall pathogenesis of these conditions. This complexity has complicated the search for susceptibility genes and has led to different but complementary approaches being used for the detection of gene effects. These include the study of monogenic cases of insulin resistance and T2DM, association studies of candidate genes and genome-wide scans. The peroxisome proliferator-activated receptor gamma (PPARgamma) and calpain-10 (CAPN10) genes have recently been identified as T2DM susceptibility genes, and the lessons learnt from these studies are helping to shape future strategies to search for additional susceptibility genes in T2DM and insulin resistance.
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PMID:Genetics of type 2 diabetes and insulin resistance: knowledge from human studies. 1220 21

Variations in the calpain-10 gene (CAPN10) have been identified among Mexican-Americans, and an at-risk haplotype combination (112/121) defined by three polymorphisms, UCSNP-43, -19, and -63, confers increased risk of type 2 diabetes. Here we examine the three polymorphisms in 1,594 Scandinavian subjects, including 409 type 2 diabetic patients, 200 glucose-tolerant control subjects, 322 young healthy subjects, 206 glucose-tolerant offspring of diabetic patients, and 457 glucose-tolerant 70-year-old men. The frequency of the 112/121 combination was not significantly different in 409 type 2 diabetic subjects compared with 200 glucose-tolerant control subjects (0.06 vs. 0.05; odds ratio 1.32 [95% CI 0.58-3.30]). In glucose-tolerant subjects, neither the single-nucleotide polymorphisms individually nor the 112/121 combination were associated with alterations in plasma glucose, serum insulin, or serum C-peptide levels at fasting or during an oral glucose tolerance test, estimates of insulin sensitivity, or glucose-induced insulin secretion. In conclusion, the frequency of the 112/121 at-risk haplotype of CAPN10 is low among Scandinavians and we were unable to demonstrate significant associations between the CAPN10 variants and type 2 diabetes, insulin resistance, or impaired insulin secretion.
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PMID:Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians. 1245 14

The 112/121 haplotype combination defined by the UCSNP-43, -19, and -63 alleles in the calpain-10 gene is associated with type 2 diabetes in Mexican Americans. To determine whether this genetic variation constitutes risk of type 2 diabetes in Japanese, we investigated its frequency in 177 patients with type 2 diabetes and 172 controls. Though this variation occurs in Japanese more frequently than in Mexican Americans, there is no significant difference in frequency between diabetic (29.9%) and control (31.9%) subjects. We also screened all exons and the putative promoter of the calpain-10 gene for mutations in 96 of the genotyped patients, resulting in the identification of 7 coding variants, including 3 missense mutations and 5 nucleotide alterations in the promoter. However, their frequencies all are similar in patients and controls, suggesting that these genetic variations are not a major factor in the occurrence of type 2 diabetes in Japanese, although they could yet be associated with various phenotypes of the disease.
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PMID:Genetic variations in calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese. 1251 60


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