Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome.

Perez-Martinez P, Delgado-Lista J, Garcia-Rios A, Ferguson JF, Gulseth HL, Williams CM, Karlström B, Kieć-Wilk B, Blaak EE, Helal O, Małczewska-Malec M, Defoort C, Risérus U, Saris WH, Lovegrove JA, Drevon CA, Roche HM, Lopez-Miranda J
Am J Clin Nutr. 2011 93 (5): 1136-41

PMID: 21389182 · DOI:10.3945/ajcn.110.010512

BACKGROUND - Calpain-10 protein (intracellular Ca(2+)-dependent cysteine protease) may play a role in glucose metabolism, pancreatic β cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism.

OBJECTIVE - The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS.

DESIGN - The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of β cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort.

RESULTS - The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele.

CONCLUSION - The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at as NCT00429195.

MeSH Terms (18)

Adult Aged Alleles Body Mass Index Calpain Cohort Studies Cross-Sectional Studies Europe Fatty Acids Female Genetic Association Studies Humans Insulin Insulin Resistance Male Metabolic Syndrome Middle Aged Polymorphism, Single Nucleotide

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