CONTEXT: 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. DESIGN: We conducted a case-control association study. SETTING: 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. PARTICIPANTS: Participants included 335 White women with PCOS and 198 White controls. MAIN MEASUREMENTS: 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.
CONTEXT: 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. DESIGN: We conducted a case-control association study. SETTING: 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. PARTICIPANTS: Participants included 335 White women with PCOS and 198 White controls. MAIN MEASUREMENTS: 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: Michelle R Jones; Lisa Italiano; Scott G Wilson; Ben H Mullin; Robert Mead; Frank Dudbridge; Gerald F Watts; Bronwyn G A Stuckey Journal: Fertil Steril Date: 2006-11 Impact factor: 7.329
Authors: Olga V Belyaeva; Sergei V Chetyrkin; Amy L Clark; Natalia V Kostereva; Karen S SantaCruz; Bibie M Chronwall; Natalia Y Kedishvili Journal: Endocrinology Date: 2007-02-08 Impact factor: 4.736
Authors: Mark O Goodarzi; Michelle R Jones; Xiaohui Li; Angela K Chua; Obed A Garcia; Yii-Der I Chen; Ronald M Krauss; Jerome I Rotter; Wendy Ankener; Richard S Legro; Ricardo Azziz; Jerome F Strauss; Andrea Dunaif; Margrit Urbanek Journal: J Med Genet Date: 2011-12-17 Impact factor: 6.318
Authors: Mark O Goodarzi; Yvonne V Louwers; Kent D Taylor; Michelle R Jones; Jinrui Cui; Soonil Kwon; Yii-Der I Chen; Xiuqing Guo; Lisette Stolk; André G Uitterlinden; Joop S E Laven; Ricardo Azziz Journal: Fertil Steril Date: 2011-04 Impact factor: 7.329
Authors: Cynthia D J Kusters; Kimberly C Paul; Aline Duarte Folle; Adrienne M Keener; Jeff M Bronstein; Lars Bertram; Johnni Hansen; Steve Horvath; Janet S Sinsheimer; Christina M Lill; Beate R Ritz Journal: Mov Disord Date: 2021-08-23 Impact factor: 9.698
Authors: Gonda Konings; Linda Brentjens; Bert Delvoux; Tero Linnanen; Karlijn Cornel; Pasi Koskimies; Marlies Bongers; Roy Kruitwagen; Sofia Xanthoulea; Andrea Romano Journal: Front Pharmacol Date: 2018-09-19 Impact factor: 5.810
Authors: Michelle R Jones; Angela Chua; Yii-Der I Chen; Xiaohui Li; Ronald M Krauss; Jerome I Rotter; Richard S Legro; Ricardo Azziz; Mark O Goodarzi Journal: PLoS One Date: 2011-05-17 Impact factor: 3.240