The distribution of FSH receptor isoforms is related to basal FSH levels in subfertile women with normal menstrual cycles

被引:57
作者
de Koning, CH
Benjamins, T
Harms, P
Homburg, R
van Montfrans, JM
Gromoll, J
Simoni, M
Lambalk, CB
机构
[1] Vrije Univ Amsterdam, Med Ctr, Div Reprod Med, Dept Obstet & Gynaecol, NL-1007 MB Amsterdam, Netherlands
[2] Univ Munster, Inst Reprod Med, D-4400 Munster, Germany
关键词
basal FSH; elevated FSH; FSH receptor; FSH receptor mutations; polymorphisms;
D O I
10.1093/humrep/dei317
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
BACKGROUND: Recently a polymorphic variant of the FSH receptor in which amino acid asparagine (Asn) at position 680 is replaced by serine (Ser) was found. This is associated with higher FSH levels in the early follicular phase and an increased FSH requirement to obtain follicular response in IVF patients. The aim of our study was to test the hypothesis that this receptor isoform occurs more often in regularly menstruating subfertility patients with elevated basal FSH than in those with normal early follicular phase FSH. METHODS: A retrospective cohort study of 38 subfertility patients with a regular menstrual cycle and elevated FSH (> 10 IU/l) compared to 40 patients with normal early follicular phase FSH was carried out. DNA was analysed to determine the FSH receptor genotype. RESULTS: The N680S variant on one or both alleles of the FSH receptor gene was significantly more prevalent in patients with elevated FSH (P < 0.05). The homozygous Asn/Asn variant at codon 680 was found in 45% of women with normal FSH and in 21% of women with elevated FSH. The homozygous Ser/Ser receptor variant was present in 12.5% of women with normal FSH and in 21% of patients with elevated FSH. Also the heterozygous combination of both variants Asn/Ser occurred more often in women with elevated FSH (58 versus 42.5%). CONCLUSIONS: The N680S sequence variation of the FSH receptor is found in > 75% of the cases with elevated basal FSH and suggests a higher FSH threshold.
引用
收藏
页码:443 / 446
页数:4
相关论文
共 30 条
[1]   Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH:: a pharmacogenetic approach to controlled ovarian hyperstimulation [J].
Behre, HM ;
Greb, RR ;
Mempel, A ;
Sonntag, B ;
Kiesel, L ;
Kaltwasser, P ;
Seliger, E ;
Röpke, F ;
Gromoll, J ;
Nieschlag, E ;
Simoni, M .
PHARMACOGENETICS AND GENOMICS, 2005, 15 (07) :451-456
[2]   Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels [J].
Check, JH ;
Peymer, M ;
Lurie, D .
GYNECOLOGIC AND OBSTETRIC INVESTIGATION, 1998, 45 (04) :217-220
[3]   Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome [J].
Conway, GS ;
Conway, E ;
Walker, C ;
Hoppner, W ;
Gromoll, J ;
Simoni, M .
CLINICAL ENDOCRINOLOGY, 1999, 51 (01) :97-99
[4]   Prediction of severity of symptoms in iatrogenic ovarian hHyperstimulation syndrome by follicle-stimulating hormone receptor Ser680 Asn polymorphism [J].
Daelemans, C ;
Smits, G ;
de Maertelaer, V ;
Costagliola, S ;
Englert, Y ;
Vassart, G ;
Delbaere, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (12) :6310-6315
[5]   Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone [J].
de Castro, F ;
Ruiz, R ;
Montoro, L ;
Pérez-Hernández, D ;
Padilla, ESC ;
Real, LM ;
Ruiz, A .
FERTILITY AND STERILITY, 2003, 80 (03) :571-576
[6]   Falsely elevated follicle-stimulating hormone levels in women with regular menstrual cycles due to interference in immunoradiometric assay [J].
de Koning, CH ;
Popp-Snijders, C ;
Martens, F ;
Lambalk, CB .
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, 2000, 17 (08) :457-459
[7]   Estimation of the follicle-stimulating hormone (FSH) threshold for initiating the final stages of follicular development in women with elevated FSH levels in the early follicular phase [J].
de Koning, CH ;
Schoemaker, J ;
Lambalk, CB .
FERTILITY AND STERILITY, 2004, 82 (03) :650-653
[8]   Elevated FSH concentrations in imminent ovarian failure are associated with higher FSH and LH pulse amplitude and response to GnRH [J].
de Koning, CH ;
Popp-Snijders, C ;
Schoemaker, J ;
Lambalk, CB .
HUMAN REPRODUCTION, 2000, 15 (07) :1452-1456
[9]   THE SIGNIFICANCE OF ELEVATED BASAL FOLLICLE-STIMULATING-HORMONE IN REGULARLY MENSTRUATING INFERTILE WOMEN [J].
EBBIARY, NAA ;
LENTON, EA ;
SALT, C ;
WARD, AM ;
COOKE, ID .
HUMAN REPRODUCTION, 1994, 9 (02) :245-252
[10]  
GEB RR, 2005, J CLIN ENDOCR METAB, V90, P4866