Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

Objectives

We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM).

Design and methods

Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects.

Results

PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all p < 0.05). The HDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all p < 0.05). PON-1 was more closely related to HDL cholesterol than to apoA-I (p = 0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both p < 0.01). The inverse relationship of PON-1 with T2DM was only modestly attenuated by HDL cholesterol or HDL particle characteristics.

Conclusions

PON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels.     

The association of HDL cholesterol concentration with the −629C>A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer

Objective. HDL cholesterol is associated with the ?629C>A cholesteryl ester transfer protein (CETP) promoter polymorphism. This relationship may in part be explained via effects on plasma cholesteryl ester transfer (CET), which reflects the activity of CETP in the context of endogenous lipoproteins, but also via CET independent pathways involved in HDL metabolism. In this study, we determined the contributions of the CETP ?629?C>A genotype, plasma CETP mass and cholesteryl ester transfer to HDL cholesterol. Material and methods. The ?629?C>A CETP gene promoter polymorphism, plasma CETP mass, CET, HDL cholesterol, lipids and apolipoprotein (apo) A‐I were measured in 220 non‐diabetic men without cardiovascular disease. Results. Plasma CETP mass (p<0.001) and CET (p<0.001) were higher, whereas HDL cholesterol (p<0.05) and plasma apo A‐I levels (p<0.05) were lower in CC compared to AA carriers. Univariate regression analysis showed that plasma CET was related to the CETP genotype (p = 0.004), plasma CETP mass (p<0.001) and triglycerides (p<0.001). In a multiple linear regression model, HDL cholesterol was related to CETP genotype (p = 0.04) and plasma triglycerides (p<0.001) without independent contributions of plasma CETP mass and CET (p>0.20 for both). Conclusions. This study suggests that, despite a relationship between a common CETP gene variation and plasma cholesteryl ester transfer, the association between CETP gene and HDL cholesterol appears to be at least in part unexplained by the plasma cholesteryl ester transfer process.     

Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure

Fanconi anemia is an autosomal recessive disease characterized by a high risk of developing bone marrow (BM) failure and acute myelogenous leukemia. We studied growth of hematopoietic progenitor cells in long- term BM culture (LTBMC) in 8 persons with Fanconi anemia and BM failure. Although LTBMC were initiated with very few BM cells, an adherent layer formed in cultures from 7 persons. In these cultures, the number of nonadherent cells increased for 10 to 15 days. Cell growth continued until cultures were terminated at day 35 to 40. During the first 2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By days 35 to 40, the adherent layer contained cells able to initiate secondary LTBMCs. These data indicate that hematopoietic precursors cells able to proliferate and differentiate in vitro are present in the BM of persons with Fanconi anemia and BM failure. They suggest that mechanisms other than absent precursor cells are responsible for BM failure in Fanconi anemia.