Chromosomal sublocalization and microsatellite DNA polymorphism of human adrenomedullin gene.
Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues such as the heart, kidney and vascular cells. We have cloned and sequenced genomic DNA encoding the human AM gene. In this study, we determined that the AM gene was located in the short arm of chromosome 11 (p15.1-3). The 3'-end of the gene is flanked by a microsatellite marker of cytosine adenine (CA) repeats. Moreover, we analyzed this DNA variation in the AM gene in the general Japanese population. Genomic DNA was obtained from the peripheral leukocytes of healthy normotensive subjects, 327 men and 149 women, aged 51 +/- 8 years (mean +/- SD). The genomic DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined via polyacrylamide gel electrophoresis (PAGE). Plasma AM concentration was measured by RIA and compared with respect to the number of CA repeats adjacent to the AM gene. In Japanese, four types of alleles with different CA-repeat numbers; 11, 13, 14 and 19, appear to exist. The frequencies of these alleles were as follows: 11 repeats, 28.8%; 13 repeats, 33.1%; 14 repeats, 35.0% and 19 repeats, 3.1%. This DNA variation does not seem to affect the transcription of the AM gene, because plasma concentrations of AM were not significantly different between the genotypes.
Ishimitsu
T
T
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, 321-0293, Mibu, Tochigi, Japan. isimitu@dokkyomed.ac.jp
Hosoya
K
K
Tsukada
K
K
Minami
J
J
Ono
H
H
Ohrui
M
M
Hino
J
J
Kangawa
K
K
Matsuoka
H
H
D053607:Adrenomedullin; D000704:Analysis of Variance; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D018900:Dinucleotide Repeats / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics*; D010455:Peptides / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic
D010455:Peptides; D053607:Adrenomedullin