Genomic structure of the FSHR and effect of the FSH-action modulating genetic variants on reproductive parameters.

A, Schematic representation of the structure of the FSHR gene drawn to an approximate scale. Exons are depicted as boxes, translated sequences are shaded in grey and transcription start-site is denoted with up-right arrow. Circle-headed bars indicate the location of FSHR SNPs -29G/A and +2039A/G (Asn680Ser); and their mutual genomic distance and linkage disequilibrium is provided. B, Distribution of the four FSHR haplotypes (G-Asn, G-Ser, A-Asn, A-Ser) formed from the FSHR -29G/A and +2039A/G (p.Asn680Ser) variants in the Baltic male cohort and Estonian oligozoospermic infertility patients (number of phased chromosomes, n = 1964 and n = 1282, respectively). C, Individual allelic effects of the FSHR -29 A-allele and FSHR 680Ser (c. +2039 G), and the cumulative haplotypic effect of the formed FSHR A-Ser gene variant on serum FSH, Inhibin B and total testes volume in the Baltic young men cohort. Results of the association testing are presented as P-values and effect sizes (regression coefficient, β) from linear regression analysis. Arrows indicate the strength and direction of the effects. D, Proportion of total phenotypic variance (%) of serum FSH, Inhibin B, total testosterone and total testes volume explained by the FSHB -211G/T (white bars), FSHR -29G/A (grey bars) and FSHR Asn680Ser (black bars) genetic variants in the Baltic young male cohort. Individual and cumulative effects of the SNPs were estimated by using the REML analysis implemented in GCTA software [33].