Abstract

Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) may play an important role in male reproduction. So far, such data for humans are not available. This study used single-nucleotide polymorphisms (SNP) to examine the association between CLOCK and semen quality in a human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 men with idiopathic infertility by SNP genotyping assays and computer-aided sperm analysis. Subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume (P=<0.001 and 0.001, respectively) compared with the TT genotype. Subjects carrying the rs3749474 CC genotype had significantly lower sperm number per ejaculate (P=0.026) and sperm motility (P=0.021) than TT genotype carriers. rs1801260 TC genotype carriers had significantly lower sperm motility compared with the TT genotype (P=0.028). For the rs3817444 genotypes, CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype (P=0.022 and 0.001, respectively). The findings suggest, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility.The gene encoding the circadian locomotor output cycles kaput protein (CLOCK) functions as an important positive enhancer of the circadian system. The observations reported in recent experimental animal studies suggested that CLOCK may play an important role in male reproduction. So far, such data for humans are not available. In this study, single-nucleotide polymorphisms (SNP) were used to examine the association between CLOCK and semen quality in human population with idiopathic infertility. Three-variant genotyping of CLOCK and semen analysis were performed in 478 males with idiopathic infertility by SNP genotyping assays and computer-assisted semen analysis. The results showed that the subjects carrying a C allele at rs3749474 (CC and TC) presented significantly lower semen volume compared with the TT genotype. For subjects carrying the CC genotype, sperm number per ejaculate and sperm motility were significantly lower compared with TT genotype carriers. The rs1801260 TC genotype carriers also had significantly lower sperm motility compared with the TT genotype. For the rs3817444 genotypes, the CA and AA genotype carriers presented significantly lower semen volume compared with the CC genotype. The findings suggested, as far as is known for the first time, an association between CLOCK genetic variants and altered semen quality in a human population with idiopathic infertility.

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