title: Genetic variation in circadian rhythm genes CLOCK and ARNTL as risk factor for male infertility.
abstract: BACKGROUND
  The circadian system has a major role in maintaining homeostasis and proper body functions including reproductive capacity. The aim of this study was to examine whether there is an association between genetic variability in the primary clock genes CLOCK and ARNTL and male infertility in humans.
  
  
  RESULTS
  We performed a case-control study, where we searched for an association between polymorphisms of CLOCK and ARNTL genes and male infertility in 961 Slovenian and Serbian Caucasian men. The study group consisted of 517 patients with idiopathic infertility and a control group of 444 fertile men. A statistically significant difference was found in genotype distribution between the two groups in the CLOCK gene: rs11932595 (p = 6·10(-5), q = 4·10(-4), OR equaled 1.9 with 95% CI 1.4-2.7), rs6811520 (p = 2·10(-3), q = 8·10(-3), OR = 1.7 with 95% CI 1.2-2.2) and rs6850524 (p = 0.01, q = 0.02, OR = 1.4 with 95% CI 1.1-1.9). Further analyses of haplotypes were consistent with genotyping results.
  
  
  CONCLUSIONS
  We provide evidence that genetic variability in the CLOCK gene might be associated with male infertility warranting further confirmation and mechanistic investigations.
authors.affiliation: Institute of Medical Genetics and Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia.
authors.forename: Alenka
authors.initials: A
authors.lastname: Hodžić
authors.forename: Momčilo
authors.initials: M
authors.lastname: Ristanović
authors.forename: Branko
authors.initials: B
authors.lastname: Zorn
authors.forename: Cane
authors.initials: C
authors.lastname: Tulić
authors.forename: Aleš
authors.initials: A
authors.lastname: Maver
authors.forename: Ivana
authors.initials: I
authors.lastname: Novaković
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000097:blood; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055771:Serbia; D017524:Slovenia; D013076:Sperm Count; D013081:Sperm Motility; D013737:Testis / Q000033:anatomy & histology; D044465:White People / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D005640:Follicle Stimulating Hormone; D056926:CLOCK Proteins; C538943:CLOCK protein, human