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Title: Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

Author
item LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ASZTALOS, BELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HOWARD, TIMOTHY - Wake Forest University
item REBOUSSIN, DAVID - Wake Forest University
item HORVATH, KATALIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SCHAEFER, ERNST - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HERRINGTON, DAVID - Wake Forest University

Submitted to: Clinical Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2009
Publication Date: 5/29/2009
Citation: Lamon-Fava, S., Asztalos, B.F., Howard, T.D., Reboussin, D.M., Horvath, K., Schaefer, E.J., Herrington, D.M. 2009. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clinical Endocrinology. 72(2):169-175.

Interpretive Summary: Recent studies have suggested that women respond differently to hormonal replacement therapy (HT), in relation to plasma lipid levels. Genetic variations in genes that regulate plasma lipid levels may be involved in the plasma lipid response to HT among women. We assessed the effect of HT on plasma levels of two types of lipoproteins: high-density lipoproteins (HDL, also called “good cholesterol”), and remnants of triglyceride-carrying lipoproteins, or RLP, which are considered atherogenic. We found that variation in the estrogen receptor gene explain part of the variability in lipid response to hormone replacement. However, most of the genes involved in lipid metabolism do not contribute to this variability.

Technical Abstract: Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the utility of glycated albumin (GA) and direct LDL-C, 2 novel assay, as compared to HbA1c and calculated LDL-C, in evaluating diabetes control and lipid in a heterogeneous population and in specific subgroups of patients with type 2 diabetes mellitus. We obtained fasting blood samples and measured HbA1c, GA, and direct LDL-C, as well as other parameters, in a multi-ethnic population of 616 male and female patients with type 2 diabetes and 895 nondiabetic controls. HbA1c and GA levels, which measure different periods of glycemia, had a correlation of r=0.70 (pb0.001), and mean values in patients were 38.7% and 43.4% higher, respectively, than controls in men, and 41.1% and 40.1% higher, respectively, than controls, in women (both pb0.001). Calculated and direct LDL-C values correlated very highly (r=0.96, pb0.001). The correlations between HbA1c and GA, and between calculated and direct LDL-C were similar for subgroups defined by gender, race, age, and other factors. Conclusions: Calculated LDL-C provides an accurate assessment of fasting LDL-C compared with a direct measurement in most subjects, except for those with hypertriglyceridemia, and GA correlates with HbA1c in diabetic and non-diabetic subjects and may serve as a reasonable marker of short term diabetic control.