PON1-108 TT and PON1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia

George Paltoglou, George Tavernarakis, Panagiotis Christopoulos, Margarita Vlassi, Maria Gazouli, Efthimios Deligeoroglou, George Creatsas, George Mastorakos
Clinical Endocrinology 2013, 79 (2): 259-66

OBJECTIVE: To investigate the frequencies of three paraoxonase (PON)1 polymorphisms in Greek polycystic ovary syndrome (PCOS) and non-PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance.

DESIGN: Case-control genetic association study.

SETTING: University Hospital Endocrine Unit.

PATIENTS: A total of 142 PCOS cases (NIH criteria) and 112 controls.

MAIN OUTCOME MEASURE: Genotyping of the c.-108C>T (PON1-108), the c.163T>A (PON1-55) and the c.575A>G (PON1-192) polymorphisms and measurement of baseline androgen and insulin resistance profile.

RESULTS: The PON1-108 TT and PON1-192 RR genotypes were more frequently encountered in the PCOS than in the control group. The PON1-192 R allele frequency was greater in the PCOS than in the control group. Comparing the PCOS and the control groups, statistical significances favoured a recessive and a dominant genetic model, respectively, for the single PON1-108 T and PON1-192 R alleles. Free Androgen Index (FAI) levels were higher in patients with PON1-108 TT, whereas Testosterone, FAI and Dehydroepiandrosterone sulphate (DHEAS) levels were higher in patients with PON1-192 RR than patients with the wild or the heterozygous genotype.

CONCLUSIONS: The decreased PON1 activity-associated PON1-108 TT and the PON1-192 RR genotypes are more frequently found in Greek PCOS women and are associated with hyperandrogenaemia. Hyperandrogenaemia must depend also on other genetic factors because the same genotypes were not associated with hyperandrogenaemia in the control group. Through identification of the involved polymorphisms, women with PCOS could potentially have a better therapeutic screening.

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