Mutation analysis of the human adipocyte-specific apM-1 gene

Background The aim of this study was to analyse the human adipocyte‐specific apM‐1 gene for sequence variations. Methods Sequence analysis was performed in 344 randomly chosen blood samples using a capillary sequencer. Results Whereas no mutations were detected in intronic regions and in 2.7 kb of t...

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Veröffentlicht in:European journal of clinical investigation 2000-10, Vol.30 (10), p.879-887
Hauptverfasser: Schäffler, A., Barth, N., Palitzsch, K-D., Drobnik, W., Schölmerich, J., Schmitz, G.
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Sprache:eng
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Zusammenfassung:Background The aim of this study was to analyse the human adipocyte‐specific apM‐1 gene for sequence variations. Methods Sequence analysis was performed in 344 randomly chosen blood samples using a capillary sequencer. Results Whereas no mutations were detected in intronic regions and in 2.7 kb of the promoter, two sequence variations were found within the coding sequence of apM‐1. For both mutations, a polymerase chain reaction‐(PCR) based restriction fragment length polymorphism (RFLP) analysis was developed, which provided a rapid screening method. A conservative T → G transition at nucleotide + 45 within exon‐2 [Gly15Gly] was detected with an allelic frequency of 0.9 for the wild‐type allele and 0.1 for the mutated allele. In addition, a missense point mutation at nucleotide + 331 within exon‐3 [Tyr111His] was detected with an allelic frequency of 0.97 for the wild‐type allele and 0.03 for the mutated allele. This mutation replaces a tyrosine by an histidine within the carboxyterminal globular domain of apM‐1. Concerning the Gly15Gly polymorphism, the TT genotype was found in 275 subjects (79.9%), the TG genotype in 67 subjects (19.5%) and the GG genotype in 2 subjects (0.6%): one with maturity onset diabetes of young age (MODY‐diabetes) and one with Lipoatrophic Diabetes Syndrome (LPDS). Concerning the Tyr111His polymorphism, the TT genotype was found in 328 subjects (95.4%), the TC genotype in 15 subjects (4.3%) and the CC genotype in 1 subject (0.3%). Conclusion The existence of two yet unknown mutations within the apM‐1 gene was demonstrated and RFLP analysis was established for rapid screening. Well defined cohorts of patients are necessary to determine the putative role of apM‐1 gene mutations in the pathogenesis of metabolic disorders.
ISSN:0014-2972
1365-2362
DOI:10.1046/j.1365-2362.2000.00722.x