Role of haptoglobin in polycystic ovary syndrome (PCOS), obesity and disorders of glucose tolerance in premenopausal women

Abstract

Background: Hp(2) alleles of the haptoglobin alpha-chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.

Methodology/principal findings: Serum haptoglobin and the haptoglobin alpha-chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp(2) alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes.

Conclusions/significance: Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp(2) alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients.

Figure 1. Serum haptoglobin, C-reactive protein and ferritin concentrations as a function of the haptoglobin genotype, obesity and glucose tolerance.

Data are means and 95% confidence intervals. The numbers below the x-axis are the number of subjects in each subgroup. *P<0.05 or less between haptoglobin genotypes; †P<0.05 or less between obese and non-obese women. ‡P<0.05 or less between women with normal or abnormal glucose tolerance.