Influence of missense mutation and silent mutation of LHβ-subunit gene in Japanese patients with ovulatory disorders

Abstract

The frequency of variant LHb containing two point mutations (T 986 -C and T 1008 -C) and its relationship to reproductive disorders differ widely between ethnic groups. In a Japanese population, variant luteinizing hormone (LH) correlates with ovulatory disorders. Here we examined the relationship between two missense mutations and five silent mutations (C 894 -T, G 1018 -C, C 1036 -A, C 1098 -T and C 1423 -T) in the LHb gene, and ovulatory disorders. We studied 43 patients with ovulatory disorders, 79 patients with normal ovulatory cycles, and 23 healthy men who agreed to join our DNA analysis. PCR-amplified LHb-subunit gene sequences were compared with a base sequence of wild-type LH reported after direct sequencing. The highest frequency (0.945) of novel allele was observed at the position of the C 1036 -A transition. No homozygotes for wild-type LHb (C 1036 ) were identified. The frequency of novel allele in patients with polycystic ovary syndrome, endometriosis, premature ovarian failure and luteal insufficiency was significantly different from that of healthy women. The frequencies of novel alleles (C 894 -T, C 1098 -T and C 1423 -T) in patients with ovulatory disorders were significantly higher than those with normal ovulatory cycles. The mean incidence of point mutation in patients with ovulatory disorders was higher than in those with normal ovulatory cycles. Among patients with variant LH, five silent mutations were identified in 87.5% of patients with ovulatory disorders, whereas only a few silent mutations were identified in patients with normal ovulatory cycles. In a Japanese population, five silent mutations of variant LH could have influenced two missense mutations and/or other unknown missense mutations, causing ovulatory disorders.

Role of luteinizing hormone β-subunit gene variants among South Indian women with polycystic ovary syndrome

“…Haploview and Pypop softwares were used to estimate LD and generate haplotype frequencies. The nucleotide positions mentioned for individual SNP is according to Takahashi et al (2003).…”

“…However, the relation between a mutant LH gene and female infertility has not yet been established clearly. While some investigators have reported the clinical significance of the variant LH in Japanese patients with reproductive disorders including infertility and/or menstrual disorders (Furui et al, 1994;Huhtaniemi et al, 1999;Takahashi et al, 2003), Finnish women carrying the variant LH (detected in 28% of the population) were reported to be fertile (Haavisto et al, 1995;Nilsson et al, 1997). Thus, evidence concerning the clinical significance of the variant LH with respect to reproductive disorders has been contradictory.…”

“…Other variants in LH β subunit gene resulting in amino-acid alterations: Glu54-Arg54 and Ser102-Gly102 as well as six silent polymorphisms have also been reported (Roy et al, 1996). Overall, there have been a limited number of studies on the mutational analysis of the LH β subunit gene (Furui et al, 1994;Liao et al, 1998;Pettersson et al, 1994;Ramanujam et al, 1999;Takahashi et al, 2003). Further, these investigations have addressed the role of LH β mutations among the infertility cases, in general, including among others, PCOS, premature ovarian failure and endometriosis.…”

FREQUENCY OF THE ALLELIC VARIANT (Trp8Arg/Ile15Thr) OF THE LUTEINIZING HORMONE GENE IN A BRAZILIAN COHORT OF HEALTHY SUBJECTS AND IN PATIENTS WITH HYPOGONADOTROPIC HYPOGONADISM

“…There have been speculative suggestions that the allelic variant Arg8/Thr15 of the LH β-subunit gene may correlate with the changes in the pituitary-gonadal function 13,18,19,22 and menstrual disorders. 14,26 Our study indicates that the allelic variant Arg8/Thr15 of the LH β-subunit gene is a polymorphism that is also commonly found in the Brazilian population.…”

“…6,[15][16][17] These polymorphisms are in complete linkage disequilibrium, and they have been found in both infertile patients and reproductively healthy subjects of several populations, with a relatively high frequency (41.9% to 53.5%) in Finnish Lapp populations and in Australian aborigines. [13][14][18][19][20][21][22][23][24][25][26][27] Latin-American populations have not been studied to date.…”