title: An avaII restriction fragment length polymorphism in the insulin-like growth factor II gene and the occurrence of smooth muscle tumors.
abstract: To detect a previously described AvaII restriction fragment length polymorphism (RFLP) in the human insulin-like growth factor II (IGF-II) gene we used the polymerase chain reaction (PCR) and genomic sequencing. The RFLP is located in exon 9 of the IGF-II gene at nucleotide 820 (GenBank accession number X07868) as a C-->T transition. Digestion with AvaII reveals a two-allele polymorphism, an a allele in which the AvaII site is not present, and a b allele. In healthy Dutch persons (n = 26), the frequency of the a allele was 62%. A similar a allele frequency was found in groups of Japanese (53%, n = 65) and Chinese (54%, n = 84), while in a French group the frequency was significantly lower (25%, n = 52). In Dutch individuals that had developed benign (n = 11; all women) and malignant (n = 9; 2 women and 7 men) smooth muscle tumors, a significantly higher frequency of 83% for the a allele was found. Since there was no difference between the presence of the a and b alleles in normal and tumor tissue of the same individual, the higher a allele frequency was not due to mutation in the IGF-II gene or loss of heterozygosity. There was no correlation between the presence of the a allele and expression of the IGF-II gene. The data reveal a correlation between homozygosity for the a allele and the occurrence of smooth muscle tumors. Women homozygous for the IGF-II a allele are more prone to develop a leiomyoma than women who are heterozygous or homozygous for the b allele. Furthermore, in both women and men the risk for leiomyosarcomas seems to be higher in a allele homozygotes.
authors.affiliation: Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Gloudemans
authors.forename: I
authors.initials: I
authors.lastname: Pospiech
authors.forename: L T
authors.initials: LT
authors.lastname: Van der Ven
authors.forename: C J
authors.initials: CJ
authors.lastname: Lips
authors.forename: W
authors.initials: W
authors.lastname: Den Otter
authors.forename: J S
authors.initials: JS
authors.lastname: Sussenbach
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007889:Leiomyoma / Q000235:genetics*; D007890:Leiomyosarcoma / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D007335:Insulin-Like Growth Factor II