WORLDWIDE FREQUENCY OF A COMMON GENETIC VARIANT OF LUTEINIZING-HORMONE - AN INTERNATIONAL COLLABORATIVE RESEARCH

Objective: To determine the worldwide frequency of a common immunologi cal LH variant because of two point mutations in the LH beta-subunit g ene (Trp8Arg and Ile15Thr). Design: Cross-sectional study on LH status (variant and wild-type) in serum (or DNA) samples from Finland (Finns and Lapps), Estonia, Poland, Sweden, The Netherlands, United Kingdom, Italy, South Africa (blacks), Thailand, China, Japan, and the United States (Hispanics and blacks). Setting: Academic research environment. Patient(s): Ambulatory adult men and women (n = 2,936) with minor ill nesses and no known endocrinological disorders. Intervention: A single blood sample was collected from each subject. Main Outcome Measure(s) : The LH status was determined by two immunofluorometric assays using monoclonal antibodies. One (assay 1) only recognizes the wild-type LH, the other (assay 2) recognizes equally variant and wild-type LH. The ratio of assay 1 to assay 2 indicates the LH status: wild-type, >0.9; heterozygote, 0.2 to 0.9; and homozygote, <0.15. One population (Lapps ) was studied by DNA analysis using polymerase chain reaction and alle le-specific oligonucleotide hybridization. Result(s): The carrier freq uency of the variant LH beta allele varied from 7.1% in U.S. Hispanics to 41.9% in Lapps of northern Finland. The variant LH beta allele ten ded to be more common in populations from Northern Europe as compared with those from Asia. Conclusion(s): The high frequency of the LH beta variant worldwide makes it an important confounding factor when obtai ning disproportionately low LH levels with some immunometric assays. T he LH variant may contribute to some pathologies of the pituitary-gona dal function. (C) 1997 by American Society for Reproductive Medicine.