Polycystic ovary syndrome (PCOS) is considered as a risk factor for diabetes type 2 (DM2), it is often associated with obesity, β-cell dysfunction or insulin resistance. Genetic factors underlying the association of PCOS with DM2 is unknown. Recent human genetic studies have revealed that transcription factor 7-like (TCF7L2) polymorphisms are associated with DM2 through modulation of β-cell function.
The aim of this study was to test if TCF7L2 polymorphisms are risk factors for impaired β-cell function, insulin sensitivity or hepatic insulin extraction in PCOS.
The study involved 109 PCOS patients and 192 control women with different glucose tolerance and BMI. Oral glucose tolerance test was performed in all subjects, in subgroup of 50 PCOS and 23 control arginin secretion test and euglycemichyperinsulinemic clamp were performed. The SNPs rs12255372, rs7901695, rs7903146 were assessed by ABI-TaqMan Genotyping Assays. Statistics (KruskalWallis one-way ANOVA) was done (NCSS-2004).
PCOS versus controls had higher BMI. To exclude the influence of BMI on metabolic parameters, we focused on lean women. Despite it lean PCOS have higher WHR and lower triglycerides than controls. PCOS have higher insulin and C-peptide secretion, impaired whole body insulin sensitivity and lower hepatic insulin extraction. The frequencies of risk aleles/haplotypes of TCF7L2 gene polymorphisms were lower in PCOS in comparision with controls. The influence of the risk TCF7L2 haplotype (CTT) on decreased insulin secretion was evident in controls during arginine test, but the secretion in lean PCOS was the same without respect of haplotype carriership. This finding could be explained by increased hepatic insulin extraction in lean PCOS carrying the risk haplotype.
The DM2 risk TCF7L2 haplotype seems to be protective in PCOS because it could normalize the increased insulin and C-peptide levels in periphery present in PCOS patients.
Study was approved by ethical committee and supported by MHCR NS/10209-3/2009 and NS/9839-4.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology