title: The reduction of Calpain-10 expression is associated with risk polymorphisms in obese children.
abstract: Excessive weight gain and obesity are major public health concerns. Childhood obesity is growing at an alarming rate. Polymorphisms in the Calpain-10 gene and the reduced expression of this gene in muscle cells and adipocytes have been associated with an increased risk of type 2 diabetes mellitus in several populations. In the present study, we explored the contribution of Calpain-10 in the development of metabolic impairment in childhood. We evaluated the presence of risk polymorphisms in the CAPN10 gene (SNP-44, SNP-43, InDel-19 and SNP-63) and the associated changes in the Calpain-10 mRNA levels in a pediatric population. A total of 161 Mexican children between 4 and 18 years old were included in this study. This population was classified into three groups according to international growth references: healthy weight (HW), overweight (OW) and obese (OB). Association studies of the anthropometric data, clinical values, genotyping and expression assays showed a decrease in the Calpain-10 mRNA and protein expression in the OW and OB groups with respect to the HW group. This decrease in the Calpain-10 mRNA expression was more evident in individuals homozygous for SNP-44 (T/T) and InDel-19 (3/3), alone (p<0.001 and p=0.015, respectively) or in combination (p=0.017). These polymorphisms were also associated with elevated BMI, weight percentiles, z-scores, waist circumferences, fasting glucose levels and beta cell functions in the OW and OB groups (p<0.05). Moreover, our results indicate a statistically significant decrease in the expression of the 75-kDa Calpain-10 isoform in the OW+OB group. The presence of polymorphisms and alterations in the expression of the CAPN10 gene at early ages might result in metabolic impairment in adulthood and should be further investigated.
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mendoza-Lorenzo
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Salazar
authors.forename: Eladio
authors.initials: E
authors.lastname: Cortes-Arenas
authors.forename: Renata
authors.initials: R
authors.lastname: Saucedo
authors.forename: Lucia
authors.initials: L
authors.lastname: Taja-Chayeb
authors.forename: Maria T
authors.initials: MT
authors.lastname: Flores-Dorantes
authors.forename: Pablo
authors.initials: P
authors.lastname: Pánico
authors.forename: Monserrat
authors.initials: M
authors.lastname: Sordo
authors.forename: Patricia
authors.initials: P
authors.lastname: Ostrosky-Wegman
mesh_terms: D000886:Anthropometry; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008800:Mexico / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D002154:Calpain; C415197:calpain 10