Key result
Non-obese, non-insulin resistant women with PCOS had significantly higher complement C3 levels (65,878 vs 45,742 RFU, p=0.001) and lower alpha-1-antitrypsin levels compared to matched controls.
Why the study?
It is unclear whether dyslipidemia frequently occurring in women with polycystic ovary syndrome is due to obesity and insulin resistance or is inherent to the condition.
Are levels of HDL-associated proteins altered in non-obese, non-insulin resistant women with PCOS compared to matched controls?
Case-Control (n=48)
No
Are levels of HDL-associated proteins altered in non-obese, non-insulin resistant women with PCOS compared to matched controls?
Absolute Event Rate: 65878% vs 45742%
p-value: p=0.001
Even in the absence of obesity and insulin resistance, women with PCOS exhibit alterations in specific HDL-associated proteins (lower alpha-1-antitrypsin and higher complement C3), suggesting an inherent increase in cardiovascular risk.
May suggest inherent HDL proteomic alterations in non-obese PCOS; hypothesis-generating and requires larger validation before any clinical inference.
Introduction: Dyslipidemia frequently occurs in women with polycystic ovary syndrome (PCOS), but it is unclear whether dyslipidemia is due to obesity and insulin resistance (IR) or is inherent to PCOS. To address this, proteomic analysis of proteins important in lipid metabolism, particularly for high-density lipoprotein cholesterol (HDL-C), was performed in non-obese, non-insulin resistant PCOS women compared to matched controls. Methods: Weight and aged-matched non-obese subjects with PCOS (n=24) and without IR were compared with control women (n=24). 19 proteins were measured by Somalogic proteomic analysis: alpha-1-antichymotrypsin, alpha-1-antitrypsin, apolipoproteins A-1, B, D, E, E2, E3, E4, L1, M, clusterin, complement C3, hemopexin, heparin cofactor-II (HCFII), kininogen-1, serum amyloid A-1, amyloid beta A-4 and paraoxonase-1. Results: Women with PCOS had a higher free androgen index (FAI) (p<0.001) and anti-Mullerian hormone (AMH) (p<0.001), but IR and C-reactive protein (CRP), a marker of inflammation, did not differ from controls (p>0.05). The triglyceride:HDL-cholesterol ratio was elevated (p=0.03) in PCOS. Alpha-1-antitrypsin levels were lower (p<0.05) and complement C3 levels were higher (p=0.001) in PCOS. C3 correlated with body mass index (BMI) (r=0.59, p=0.001), IR (r=0.63, p=0.0005) and CRP (r=0.42, p=0.04) in women with PCOS, though no correlations of these parameters with alpha-1-antitrypsin were found. Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and levels of the other 17 lipoprotein metabolism-associated proteins did not differ between the two groups (p>0.05). However, in PCOS, alpha-1-antichymotrypsin correlated negatively with BMI (r=-0.40, p<0.04) and HOMA-IR (r=-0.42, p<0.03), apoM correlated positively with CRP (r=0.36, p<0.04) and HCFII correlated negatively with BMI (r=-0.34, p<0.04). Conclusion: In PCOS subjects, when obesity, IR and inflammation confounders were absent, alpha-1-antitrypsin was lower and complement C3 was higher than in non-PCOS women, suggesting increased cardiovascular risk; however, subsequent obesity related IR/inflammation likely stimulates other HDL-associated protein abnormalities, thus increasing cardiovascular risk further.
No takes yet. Share an insight, caveat, or question.
Butler et al. (2023) conducted a case-control in Polycystic ovary syndrome (n=48). Polycystic ovary syndrome vs. Matched control women without PCOS was evaluated on Complement C3 levels (RFU) (p=0.001). Non-obese, non-insulin resistant women with PCOS had significantly higher complement C3 levels (65,878 vs 45,742 RFU, p=0.001) and lower alpha-1-antitrypsin levels compared to matched controls.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: