title: Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome.
abstract: BACKGROUND
  Decreased sex hormone-binding globulin (SHBG) levels were associated with polycystic ovary syndrome (PCOS). SHBG polymorphisms associated with reduced SHBG production were tested for their association with PCOS, but with inconclusive results. We tested whether altered SHBG levels and SHBG variants were associated with PCOS.
  
  
  METHODS
  The study subjects included 242 women with PCOS and 238 control women. SHBG genotyping was done by real-time PCR.
  
  
  RESULTS
  Higher minor allele frequency of rs13894, rs858521 and rs727428 was seen in PCOS cases, and significant differences in rs858521 and rs727428 genotypes distribution were seen between PCOS cases and controls. Multivariate regression analysis confirmed the association of only rs727428 with PCOS. Though it was not statistically significant, serum SHBG levels were reduced according to rs727428 genotypes in PCOS cases than in controls. Carriage of rs727428 minor allele was associated with significant increases in free/bioactive testosterone in PCOS cases. Seven-locus (rs9898876-rs13894-rs858521-rs1799941-rs6257-rs6259-rs727428) haploview analysis showed increased frequency of GCCGTGA, GTCGTGA and GTCATGG, and reduced frequency of GTCGTGG haplotypes in PCOS cases than in controls, thus conferring disease susceptibility and protective nature to these haplotypes, respectively.
  
  
  CONCLUSIONS
  Specific SHBG variants affecting serum SHBG levels and SHBG haplotypes are associated with PCOS, suggesting the role for SHBG as PCOS candidate gene.
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Tala M
authors.initials: TM
authors.lastname: Abu-Hijleh
authors.forename: Emily
authors.initials: E
authors.lastname: Gammoh
authors.forename: Amna S
authors.initials: AS
authors.lastname: Al-Busaidi
authors.forename: Zainab H
authors.initials: ZH
authors.lastname: Malalla
authors.forename: Samira
authors.initials: S
authors.lastname: Madan
authors.forename: Naeema
authors.initials: N
authors.lastname: Mahmood
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001445:Bahrain; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007328:Insulin / Q000097:blood; D016015:Logistic Models; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D007328:Insulin; D012738:Sex Hormone-Binding Globulin