calpain and Diabetes--Gestational

Several polymorphisms have been identified in transcription factor 7-like 2 (TCF7L2), and calpain-10 (CAPN10) genes. Controversial conclusions for the genetic relationship between these polymorphisms and gestational diabetes mellitus (GDM) risks were obtained. Our study aims at assessing whether these polymorphisms are associated with GDM susceptibility via a meta-analysis. A total of 19 eligible case-control articles were obtained after databases searching. A significantly increased GDM risk was observed for TCF7L2 rs7903146 (all OR > 1, p < 0.01), but not rs12255372. In addition, significant difference was observed in case/control comparison for 112/112 (GG/2R2R/TT) haplotype combination frequency of CAPN10 SNP-43/19/63 (OR = 3.32, p = 0.043). In summary, TCF7L2 rs7903146 and 112/112 haplotype of CAPN10 might be associated with GDM risks.

Topics: Adult; Calpain; Case-Control Studies; Diabetes, Gestational; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors; Transcription Factor 7-Like 2 Protein

The purpose of the meta-analysis is to evaluate the association between calpain-10 (CANP10) gene polymorphisms and gestational diabetes mellitus (GDM).. A computer-based retrieval was performed in Web of Science, Embase and PubMed databases for eligible studies. The genotype data from four variants in CANP10 [single-nucleotide polymorphisms (SNP) 19, 43, 44, and 63] were collected. The pooled Odds ratios (ORs) with 95 % confidence intervals (CI) were conducted for five genetic models.. Five studies containing 1003 GDMs and 1788 controls are included in this meta-analysis. The overall combined odds ratios show that SNP 19 and SNP 43 are not associated with increased risk of GDM in all genetic models. The association between SNP 63 and GDM is only significant in the heterozygous model (OR 2.79, 95 % CI 1.15-6.74). The SNP 44 is associated with increased risk of GDM in the recessive model (OR 1.75, 95 % CI 1.07-2.85), but only two studies are included.. This meta-analysis indicates that women carriage of TT genotype in SNP 63 (rs5030952) is associated with increased risk in GDM.

Topics: Calpain; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors

BACKGROUND This study aimed to investigate the association between the rs2975760 and rs3792267 single nucleotide polymorphisms (SNPs) of the calpain 10 (CAPN10) gene and gestational diabetes mellitus. MATERIAL AND METHODS The study included 138 patients with gestational diabetes mellitus and 152 healthy pregnant women. Venous blood was separated, and the DNA was extracted. The rs2975760 and rs3792267SNP polymorphisms of CAPN10 were detected using polymerase chain reaction (PCR). The frequencies of different genotypes in patients with gestational diabetes mellitus and healthy pregnant women were determined, and the relationship between different SNP genotypes and the risk of gestational diabetes mellitus was analyzed. RESULTS There were no significant differences in the frequencies of the TT, CT and CC genotypes of rs2975760 and the frequencies of the GG, AG and AA genotypes of rs3792267 between the women with gestational diabetes and the controls. Expression of rs2975760 and rs3792267 were not associated with the risk of gestational diabetes in the dominant model, recessive model, and additive model. However, grade B and grade D diabetes in the CC and TC genotypes of rs2975760 were significantly different from those in the TT genotype (P<0.05). Grade B and grade D diabetes in the AA and AG genotypes of rs3792267 were significantly different compared with those in the GG genotype (P<0.05), and allele A was significantly increased compared with allele G (P<0.05). CONCLUSIONS The rs2975760 and rs3792267 SNP polymorphisms of CAPN10 showed no significant association with the incidence of gestational diabetes mellitus and only a mild association with the severity.

Topics: Adult; Alleles; Asian People; Calpain; Case-Control Studies; China; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays.  The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Topics: Adolescent; Adult; Blood Glucose; Calpain; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; INDEL Mutation; Mexico; Middle Aged; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors; Young Adult

In several large studies an association between certain single-nucleotide polymorphisms (SNP) of the calpain-10 gene (CAPN10) with type 2 diabetes mellitus (T2D) has been identified. Since T2D and gestational diabetes mellitus (GDM) seem to be linked pathophysiologically, we examined the frequencies of CAPN10-polymorphisms in women with GDM.. By using real-time PCR assisted melting curve analysis samples of 204 women with GDM and 297 controls were tested for variations of SNP-43, -44, -63 and Indel-19 of CAPN10.. Since the genotype frequencies found in SNP-44 among the controls did not meet the Hardy-Weinberg-Equilibrium, the further analysis was performed with SNP-43, -63 and Indel-19 only. Herein, the distribution of neither genotype nor allele nor haplogenotype-combination nor haplotype showed a significant difference between both groups.. Variations of SNP-43, -63 and Indel-19 of CAPN10 were not associated with an increased risk of developing GDM.

Topics: Adult; Calpain; Case-Control Studies; Diabetes, Gestational; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Humans; INDEL Mutation; Middle Aged; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors

Topics: Calpain; Diabetes, Gestational; Female; Genotype; Haploidy; Humans; Polymorphism, Single Nucleotide; Pregnancy

To study three single nucleotide polymorphisms (SNP), SNP-43, -19 and -63 of calpain-10 (CAPN10) gene in pregnant women with glucose metabolism disorders and their relationship with the risk of these disorders.. Totally, 270 pregnant women including 156 with an abnormal oral glucose tolerance test (study group) and 114 healthy controls were selected among those delivered at the Department of Obstetrics and Gynecology, Peking University First Hospital from Jan. 2005 to Dec. 2006. The SNP of CAPN10 gene at positions 43, 19, and 63 were analyzed by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR).. (1) The frequencies CAPN10 SNP-19 2R/2R genotype (26.9%, 42/156) and 2R allele (48.9%, 152/312) were higher than those in controls (12.3%, 14/114 and 36.8%, 84/228, respectively; P=0.012, 0.006). (2) Stratified analysis according to family history of diabetes mellitus showed the proportion of the CAPN10 SNP-19 2R/2R+2R/3R genotypes (83%, 47/57) in the study group were significantly higher than that of control group (52%, 11/21; P=0.009), and the proportion of SNP-63 T/T+T/C genotypes (47%, 27/57) in study group were significantly higher than that of control group (14%, 3/21; P=0.026) among those with positive family history. (3) The combined effect of CAPN10 SNP-43, -19 and -63 on glucose metabolism disorders was analyzed by comparing with the other haplotypes and showed that the haplotype 121 distribution in study group was significantly higher than those in controls (P=0.036), and 221 haplotype was significantly lower than controls (P=0.042).. (1) CAPN10 SNP-19 is associated with glucose metabolism disorders in pregnant women. And 2R allele might be the risk factor. CAPN10 SNP-19 2R/2R+2R/3R and SNP-63 T/T+T/C genotypes might increase the risk of glucose metabolism disorders in women with positive family history. Haplotype 121 might increase the risk of glucose metabolism disorders in pregnant women and 221 be a protective factor.

Topics: Adult; Alleles; Blood Glucose; Calpain; Case-Control Studies; Diabetes, Gestational; DNA Primers; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glucose Metabolism Disorders; Haplotypes; Humans; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Complications; Risk Factors

Gestational diabetes mellitus (GDM) and type 2 diabetes share a common pathophysiological background, including beta cell dysfunction and insulin resistance. In addition, women with GDM are at increased risk of developing type 2 diabetes later in life. Our aim was to investigate whether, like type 2 diabetes, GDM has a genetic predisposition by studying five common polymorphisms in four candidate genes that have previously been associated with type 2 diabetes.. We studied 1,777 unrelated Scandinavian women (588 with GDM and 1,189 pregnant non-diabetic controls) for polymorphisms in the genes encoding potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11 E23K), insulin receptor substrate 1 (IRS1 G972R), uncoupling protein 2 (UCP2 -866G-->A) and calpain 10 (CAPN10 SNP43 and SNP44).. The EE, EK and KK genotype frequencies of the KCNJ11 E23K polymorphism differed significantly between GDM and control women (31.5, 52.7 and 15.8% vs 37.3, 48.8 and 13.9%, respectively; p=0.050). In addition, the frequency of the K allele was increased in women with GDM (odds ratio [OR]=1.17, 95% CI 1.02-1.35; p=0.027), and this effect was greater under a dominant model (KK/EK vs EE) (OR=1.3, 95% CI 1.05-1.60; p=0.016). Analysis of the IRS1 G972R polymorphism showed that RR homozygosity was found exclusively in women with GDM (91.0, 8.3 and 0.7% vs 90.7, 9.3 and 0.0% for GG, GR and RR genotypes, respectively; p=0.014). The genotype and allele frequencies of the other polymorphisms studied were not statistically different between the GDM and control women.. The E23K polymorphism of KCNJ11 seems to predispose to GDM in Scandinavian women.

Topics: Adult; Alleles; Calpain; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin-Secreting Cells; Ion Channels; Membrane Transport Proteins; Mitochondrial Proteins; Odds Ratio; Phosphoproteins; Polymorphism, Genetic; Potassium Channels, Inwardly Rectifying; Pregnancy; Risk; Sweden; Uncoupling Protein 2

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. Epidemiologic and pathophysiologic data suggest a close link of this disease to non-insulin-dependent diabetes mellitus. Within the calpain-10 gene various single-nucleotide polymorphisms have been identified that increased the risk for non-insulin-dependent diabetes mellitus. Therefore, we examined single-nucleotide exchanges of this gene in women with GDM.. A total of 875 unselected women were prospectively screened for GDM. Eighty women of this population, 40 patients with an abnormal oral glucose tolerance test and 40 normal controls, were randomly selected. DNA samples isolated from sera of the control and study groups were analyzed with respect to single-nucleotide polymorphisms of the calpain-10 gene at positions 43, 19, and 63 using polymerase chain reaction amplification and restriction analysis.. Women with GDM were more likely to be homozygous for the allele 1 of single-nucleotide polymorphism 63 (P =.02 by chi(2) test). With respect to single-nucleotide polymorphisms 19 and 43, no significant differences in allele distribution were detected between controls and women with GDM. When comparing the different haplotypes for calpain-10 (single-nucleotide polymorphisms 43, 19, and 63), all women with the haplotype combination 121/221 (n = 8) had gestational diabetes (P =.005 by Fisher exact test).. Our results indicate that the haplotype 121/221 of the calpain-10 gene may be associated with disturbances of glucose metabolism during pregnancy.. II-1

Topics: Adult; Body Mass Index; Calpain; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Tolerance Test; Haplotypes; Humans; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Pregnancy