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**6** 

*USA* 

**Dyslipidemia: Genetics and Role** 

Nora L. Nock and Aiswarya L.P. Chandran Pillai

Dyslipidemia is characterized by an aggregation of lipoprotein abnormalities including low high density lipoprotein cholesterol (HDL-C), high serum triglycerides (TG) and increased small low density lipoprotein cholesterol (LDL-C). Lipoproteins, which contain lipids and proteins (apolipoproteins, APO) are responsible, primarily, for transporting water insoluble lipids (cholesterol, TG) in plasma from the intestines and liver, where they are absorbed and synthesized, respectively, to peripheral tissues (muscle, adipose) for utilization, processing and/or storage (Kwan et al., 2007). There are several subtypes of lipoproteins with specific functions including, from smallest to largest: 1) chylomicrons, which transport dietary TG from the intestines to the peripheral tissue and liver; 2) very LDL (VLDL) particles, which transport TG from the liver to peripheral tissues; 3) intermediate density lipoproteins (IDL), which are produced from VLDL particle metabolism and may be taken up by the liver or further hydrolyzed to LDL; and, 4) HDL, which is key in 'reverse cholesterol transport' or

The Metabolic Syndrome (MetSyn) is a clustering of traits including dyslipidemia as well as hypertension (raised systolic and/or diastolic blood pressure), dysglycemia (high fasting glucose) and obesity (high body mass index (BMI) and/or waist circumference). Dyslipidemia is formally defined within the context of MetSyn. Various diagnostic definitions have been proposed for MetSyn by several organizations including the World Health Organization (WHO) (Alberti and Zimmet, 1998), European Group Insulin Resistance (EGIR) (Balkau and Charles, 1999), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III, (2001), International Diabetes Federation (IDF, (Alberti et al., 2005), American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) (Grundy et al., 2006) and, with the most recent joint interim statement proposed by the AHA/NHLBI, IDF and other organizations (Alberti et al., 2009). Although the recommendations differ widely on the obesity component, the dyslipidemia component has been fairly consistently defined as having TG ≥ 150 mg/l, HDL-C <40 mg/dL (1.03 mmol/l, in males) or <50 mg/dL (1.29 mmol/l in females) or drug treatment for elevated TG or low HDL-C (NCEP ATP III: (2001), IDF: (Alberti et al., 2005), Joint Statement: (Alberti et al., 2009)). However, the WHO (Alberti and Zimmet, 1998) proposed slightly lower limits for HDL-C (male: < 0.9 mmol/l (35 mg/dl); female: < 1.0 mmol/l (39 mg/dl)) and the EGIR (Balkau and Charles, 1999) recommended dyslipidemia be defined by HDL-C < 1.0 mmol/l (39 mg/dl) or TG > 2.0 mmol/l (177 mg/dl). There is currently no recommended value for

shuttling cholesterol from peripheral cells to the liver (Kwan et al., 2007).

**1. Introduction** 

**in the Metabolic Syndrome** 

*Case Western Reserve University* 

