**4.2 Genetic variation in enzymes and transcription factors and TG levels**

As mentioned above (see Section 2.1), LPL is an enzyme that hydrolyzes TG-rich particles in peripheral tissues (muscle, macrophages, adipose) generating FFA and glycerol for energy metabolism and storage (Goldberg, 1996). More than 100 mutations in LPL have been identified (Murthy et al., 1996); however, only a few common nonsynonymous SNPs have been consistently associated with TG levels including rs1801177, rs328 and rs268 (Mailly et al., 1995; Rip et al., 2006; Sagoo et al., 2008; Teslovich et al., 2010; Willer et al., 2008). Two SNPs, rs1801177 and rs328, have also been consistently associated with CHD; however, there is fairly strong LD between these SNPs, at least in Caucasians (Sagoo et al., 2008).

MLX interacting protein like (MLXIPL) locus encodes a transcription factor of the Myc/Max/Mad superfamily which activates, in a glucose-dependent manner, carbohydrate response element binding protein (CREBP) that is expressed in lipogenic tissues coordinating the subsequent activation of lipogenic enzymes such as fatty acid synthase (FAS) to convert dietary carbohydrate to TG (Iizuka and Horikawa, 2008). The human MLXIPL gene is located on chromosome 7 (7q11.23). Although initially identified through GWAS, the rs1745738 polymorphism has been replicated in other studies (Johansen and Hegele, 2011; Teslovich et al., 2010; Wang et al., 2008; Willer et al., 2008).
