title: No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity.
abstract: In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association.
authors.affiliation: Department of Child and Adolescent Psychiatry of the Philipps University Marburg, Clinical Research Group, Schützenstr. 49, Germany. anke.hinney@med.uni-marburg.de
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Benjamin
authors.initials: B
authors.lastname: Antwerpen
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.forename: Helmut
authors.initials: H
authors.lastname: Schäfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Siegfried
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D002154:Calpain / Q000235:genetics*; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D002154:Calpain; C415197:calpain 10