title: Independent confirmation of association between metabolic phenotypes of polycystic ovary syndrome and variation in the type 6 17beta-hydroxysteroid dehydrogenase gene.
abstract: BACKGROUND
  Few candidate genes for polycystic ovary syndrome (PCOS) are widely agreed upon largely due to lack of replication. Type 6 17beta-hydroxysteroid dehydrogenase (HSD17B6) gene expression is increased in PCOS ovarian theca. Previous genetic study of HSD17B6 reported significant association of rs898611 with PCOS risk and metabolic phenotypes.
  
  
  OBJECTIVE
  Our objective was to replicate association between polymorphisms in HSD17B6 and PCOS in a well-characterized replication cohort.
  
  
  METHODS
  We conducted a case-control association study.
  
  
  METHODS
  Subjects were recruited from reproductive endocrinology clinics; controls were recruited from the surrounding communities of the University of Alabama at Birmingham and Cedars-Sinai Medical Center in Los Angeles. Genotyping occurred at Cedars-Sinai Medical Center.
  
  
  METHODS
  Participants included 335 White women with PCOS and 198 White controls.
  
  
  METHODS
  We assessed HSD17B6 genotype, PCOS status, and metabolic traits.
  
  
  RESULTS
  The minor allele of rs898611 was not associated with PCOS; however, it was associated with increased body mass index (P = 0.031), increased fasting insulin (P = 0.008), decreased fasting glucose/insulin ratio (P = 0.038), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.021). rs10459247 and rs10876920 were associated with increased fasting insulin (P = 0.031 and 0.019, respectively), and rs10876920 was also associated with increased HOMA-IR (P = 0.046). Haplotype T-A-T-C was associated with reduced fasting insulin (P = 0.046), and haplotype C-A-C-T was associated with increased body mass index (P = 0.032).
  
  
  CONCLUSIONS
  Although we did not replicate association between PCOS and rs898611, we replicated associations of this variant and others in HSD17B6 with metabolic traits. These replication data suggest a role for HSD17B6 in PCOS. How HSD17B6, an enzyme involved in steroid metabolism, may influence BMI and insulin resistance in PCOS remains to be determined.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Jones
authors.forename: Ruchi
authors.initials: R
authors.lastname: Mathur
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000097:blood; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D019998:Racemases and Epimerases / Q000235:genetics*; D012306:Risk; D013256:Steroids / Q000378:metabolism; D044465:White People
chemical_list: D007328:Insulin; D013256:Steroids; C414602:HSD17B6 protein, human; D019998:Racemases and Epimerases