Low-density lipoprotein receptor–related protein-5 C/T polymorphism in exon 18 is associated with C peptide and proinsulin levels in control women and patients with polycystic ovary syndrome

Objective

To assess the previously unstudied potential role of C/T (A1330V) polymorphism of the low-density lipoprotein receptor–related protein-5 gene in insulin sensitivity and secretion in polycystic ovary syndrome. The low-density lipoprotein receptor–related protein-5 gene has been found to play a role in determining insulin secretion in animal models.

Design

Case–control study.

Setting

Tertiary outpatient clinic.

Patient(s)

Women with polycystic ovary syndrome (n = 299; age, 27.5 ± 7.1 y [mean ± SD]), according to the European Society of Human Reproduction and Embryology criteria, as well as healthy control women (n = 187, age, 28.9 ± 9.8 y).

Intervention(s)

Oral glucose tolerance test, blood sampling.

Main Outcome Measure(s)

Glucose, insulin, C peptide, proinsulin during oral glucose tolerance tests, and lipids. Genotyping of C/T (A1330V) polymorphism by polymerase chain reaction–restriction fragment length polymorphism.

Result(s)

There was no difference in the frequency of genotypes between women with polycystic ovary syndrome (CC/CT/TT: 80.3%, 18.4%, 1.3%) and the control women (79.1%, 19.8%, and 1.1%). Carriers of the T allele had statistically significantly higher basal and stimulated C peptide and proinsulin levels than CC homozygotes, both basally and at the 180th minute. Regarding insulin sensitivity, there was no difference between T carriers and CC homozygotes.

Conclusion(s)

Polymorphism of C/T in the low-density lipoprotein receptor–related protein-5 gene is associated with C-peptide and proinsulin secretion but does not influence insulin sensitivity in either healthy women or women with polycystic ovary syndrome.

Key Words: Polycystic ovary syndrome, C peptide, proinsulin, insulin resistance, LRP5 gene, genetic polymorphism