title: Association of common LH variant with hyperfunctional promoter in a Japanese infertile woman.
abstract: A common LH variant (V-LH) with Trp8Arg and Ile15Thr is often associated with ovarian dysfunction primarily in the Japanese population, and the LHB gene encoding V-LH is linked with a hyperfunctional promoter that could partly compensate for the somewhat weak biological effect of the V-LH in the Finnish and other several populations. We analyzed the promoter region in a Japanese infertile woman homozygous for the V-LH, to examine whether the hyperfunctional promoter is present or absent in the Japanese V-LH carriers with ovarian dysfunction. Direct sequencing was performed for a 661 bp promoter region from -8 to -668 bp of LHB, revealing homozygosity for eight nucleotide substitutions (-238A>G, -276G>A, -489C>A, -490T>A, -504T>A, -506T>C, -525T>G, and -552C>T) that are identical to those found in the hyperfunctional promoter. The results suggest that ovarian dysfunction frequently observed in the Japanese V-LH carriers would be due to some population-specific genetic and/or environmental factor(s) rather than to the lack of the hyperfunctional promoter and the resultant low biological effect of the V-LH. In addition, the tight linkage between the two missense substitutions in the coding region and the eight nucleotide substitutions in the promoter region of LHB appears to be common to various ethnic groups.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo.
authors.forename: Shunyu
authors.initials: S
authors.lastname: Liu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Bunpei
authors.initials: B
authors.lastname: Ishizuka
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D007247:Infertility, Female / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
chemical_list: D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA