Muramatsu Y, etal., IUBMB Life 2003 Sep;55(9):533-7.
The rat strain Otsuka Long-Evans Tokushima Fatty (OLETF) is an animal model for type 2 diabetes mellitus. Nidd8/of has been identified as one of 14 quantitative trait loci (QTLs) involved in the diabetes by a whole genome search in 160 F2 progenies obtained by mating the OLETF and F344 rats. Compara
tive mapping between human and rat indicated that the Nidd8/of genomic region, near D9rat21 on rat chromosome 9, contains the calpain10 (Capn10) gene, which is putative type 2 diabetes-susceptibility gene in humans. In this study, we found no difference in Capn10 mRNA expression in the heart, liver, skeletal muscle and pancreas between OLETF and F344 rats at 5 and 10 weeks of age. However, we found a single nucleotide polymorphism (SNP) (A/A genotype in OLETF and G/G genotype in F344 and LETO rats) at the base 583 downstream from the translation start site in the rat Capn10 cDNA sequence. This SNP was deduced to substitute serine (OLETF) for glycine (F344 and LETO) at the 195 amino acid residue within the protease domain of rat Capn10. Because serine is generally not interchangeable with glycine in respect of the protein structure and function, it was deduced that the A/A genotype in OLETF is not a 'safe' mutation. This non-conservative amino acid substitution might be associated with susceptibility to type 2 diabetes in OLETF rats.
Guevara-Cruz M, etal., Nutr Hosp. 2014 Sep 1;30(3):671-7. doi: 10.3305/nh.2014.30.3.7611.
Dyslipidemia is a major public health problem, and therefore, it is important to develop dietary strategies to diminish the prevalence of this disorder. It was recently reported that diet may play an important role in triggering insulin resistance by interacting with genetic variants at the CAPN10
tyle='font-weight:700;'>CAPN10 gene locus in patients with metabolic syndrome. Nonetheless, it remains unknown whether genetic variants of genes involved in the development of type 2 diabetes are associated with variations in high-density lipoprotein cholesterol (HDL-C). The study used a single-center, prospective, cohort design. Here, we assessed the effect of four variants of the CAPN10 gene on HDL-C levels in response to a soy protein and soluble fiber dietary portfolio in subjects with dyslipidemia. In 31 Mexican dyslipidemic individuals, we analyzed four CAPN10 gene variants (rs5030952, rs2975762, rs3792267, and rs2975760) associated with type 2 diabetes. Subjects with the GG genotype of the rs2975762 variant of the CAPN10 gene were better responders to dietary intervention, showing increased HDL-C concentrations from the first month of treatment. HDL-C concentrations in participants with the wild type genotype increased by 17.0%, whereas the HDL-C concentration in subjects with the variant genotypes increased by only 3.22% (p = 0.03); the low-density lipoprotein cholesterol levels of GG carriers tended to decrease (-12.6%). These results indicate that Mexican dyslipidemic carriers of the rs2975762-GG genotype are better responders to this dietary intervention.
BACKGROUND: Essential hypertension (EH) is a common disorder, which can increase the risk for type 2 diabetes (T2D). Calpain-10 (CAPN10) gene was the first candidate gene of T2D identified through genome-wide linkage and positional cloning, but few works have f
ocused on the relationship of CAPN10 with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) in EH patients. METHODS: To identify the effect of UCSNP-43 and UCSNP-44 in CAPN10 gene on susceptibility to IFG/IGT, we conducted a case-control study in 961 EH patients with and without IFG/IGT among Han Chinese population. We also evaluated the impact of two SNPs on insulin sensitivity and glucose tolerance estimated through oral glucose tolerance test and renal functions by blood chemical assays. RESULTS: The major findings of this study were that UCSNP-43 displayed higher G120 and AUCg. In addition, UCSNP-44 was found associated with IFG/IGT in EH patients, and associated with increased G30, G60, AUCg, Cederholm index, Scr and eGFR. The haplotype UCSNP-43-44 was detected associated with IFG/IGT susceptibility, G60, G120, I0, AUCg, Scr and eGFR by the linear regression with the adjustment for sex, age, BMI, mean blood pressures and ACEI/ARB treatment. CONCLUSIONS: These findings provided some evidence that CAPN10 gene may play an important role in the pathogenesis of IFG/IGT in EH patients.
Li YY, etal., Endocr J. 2015;62(2):183-94. doi: 10.1507/endocrj.EJ14-0297. Epub 2014 Nov 8.
A correlation between the single nucleotide polymorphism (SNP)43 G>A in the calpain-10 (CAPN10) gene (i.e., CAPN10 SNP43) and type 2 diabetes mellitus (T2DM) susceptibility has been suggested, but the evidence for such a rel
ationship remains controversial. To explore the association of the CAPN10 SNP43 with T2DM in Asian populations, a meta-analysis including 9,353 participants from 20 individual studies in Asian populations was conducted. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by a fixed-effect model or random-effect model. The relationship between CAPN10 SNP43 and T2DM was significant under allelic (OR: 1.18, 95% CI: 1.01-1.38, P = 0.03), recessive (OR: 1.236, 95% CI: 1.038-1.472, P =0.017), heterozygous (OR: 1.261, 95% CI: 1.053-1.512, P = 0.012), and additive (OR: 1.183, 95% CI: 1.014-1.381, P = 0.033) genetic models but not under dominant (OR: 1.12, 95% CI: 0.78-1.62, P = 0.53) or homozygous (OR: 0.937, 95% CI: 0.648-1.355, P = 0.730) genetic models. CAPN10 SNP43 was significantly associated with T2DM susceptibility in Asian populations, especially in Chinese populations. Asians, particularly Chinese people with the SNP43 G allele of the CAPN10 gene may have an increased risk of developing T2DM.
