Lipoprotein(a) and apolipoprotein(a) in polycystic ovary syndrome

Abstract

Objective: Levels of lipoprotein(a), Lp(a), an independent risk factor for cardiovascular disease (CVD), are affected by sex hormones. Women with polycystic ovary syndrome (PCOS) have elevated androgen levels and are at increased CVD risk. We investigated the impact of PCOS-related hormonal imbalance on Lp(a) levels in relation to apo(a) gene size polymorphism, a major regulator of Lp(a) level.

Design: Cross-sectional.

Patients: Forty-one Caucasian women with PCOS based on the NIH criteria.

Measurements: (1) Apo(a) gene size polymorphism measured as Kringle (K) 4 repeat number; (2) total plasma Lp(a) level; (3) allele-specific apo(a) level assessing the amount of Lp(a) carried by an individual apo(a) allele/isoform; and (4) sex hormone levels.

Results: The mean age was 32 ± 6 years, and the mean BMI was 35 ± 8 with 66% of women classified as obese (BMI >30 kg/m² ). LDL cholesterol was borderline high (3·37 mmol/l), and HDL cholesterol was low (1·06 mmol/l). The distribution of Lp(a) level was skewed towards lower levels with a median level of 22·1 nmol/l (IQR: 6·2-66·5 nmol/l). Lp(a) levels were not correlated with age, body weight or BMI. The median allele-specific apo(a) level was 10·6 nmol/l (IQR: 3·1-31·2 nmol/l), and the median apo(a) size was 27 (IQR: 23-30) K4 repeats. Allele-specific apo(a) levels were significantly and inversely correlated with K4 repeats (r = -0·298, P = 0·007). Neither Lp(a) nor allele-specific apo(a) levels were significantly associated with testosterone or dehydroepiandrosterone sulphate levels.

Conclusions: The apo(a) genetic variability remains the major regulator of plasma Lp(a) levels in women with PCOS.

Figure 1. Distributions of Lp(a) levels (A), allele-specific apo(a) levels (B) and correlations of allele-specific apo(a) levels with apo(a) size polymorphism (C) in PCOS women

Allele-specific apo(a) level was determined as described in the Materials and Methods section. More information on the determination of allele-specific apo(a) levels can be found in reference #. Pearson’s correlation analysis with square-root transformed allele-specific apo(a) level was used to describe the relationship with apo(a) size polymorphism.

Figure 2. Distribution of smaller apo(a) dominance pattern in PCOS women vs. women at risk for CHD or healthy women

Data for women at risk for CHD was from reference #. Data for healthy women was based on unpublished observation from our laboratory. Apo(a) dominance pattern was assessed as described in the Materials and Methods section.