title: Is the association between insulin resistance and diabetogenic haematopoietically expressed homeobox (HHEX) polymorphism (rs1111875) affected by polycystic ovary syndrome status?
abstract: Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P<0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33-0.78; P=0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status.
authors.affiliation: Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Arabi Street - Yemen Street - Velenjak - Tehran, 1985717413, Islamic Republic of Iran.
authors.forename: F Ramezani
authors.initials: FR
authors.lastname: Tehrani
authors.affiliation: Cellular and Molecular Endocrine Research Center, Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Arabi Street - Yemen Street - Velenjak - Tehran, 1985717413, Islamic Republic of Iran.
authors.forename: M
authors.initials: M
authors.lastname: Zarkesh
authors.affiliation: Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Arabi Street - Yemen Street - Velenjak - Tehran, 1985717413, Islamic Republic of Iran.
authors.forename: M
authors.initials: M
authors.lastname: Tohidi
authors.affiliation: Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Arabi Street - Yemen Street - Velenjak - Tehran, 1985717413, Islamic Republic of Iran.
authors.forename: F
authors.initials: F
authors.lastname: Azizi
authors.affiliation: Cellular and Molecular Endocrine Research Center, Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Arabi Street - Yemen Street - Velenjak - Tehran, 1985717413, Islamic Republic of Iran.
authors.forename: A
authors.initials: A
authors.lastname: Zadeh-Vakili
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C078492:HHEX protein, human; D018398:Homeodomain Proteins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors