1595C>G or LPL Ser447X
Allele frequency in population:
According to the 1000 Genomes database, the minor G allele has a frequency of 9% in the general population.
Genes & SNP Summary
LPL encodes the enzyme, lipoprotein lipase, which is responsible for the hydrolysis of triglycerides and very low-density lipoproteins (VLDL). The LPL C>G, also called Ser447X, polymorphism has been repeatedly shown in the literature to be associated with triglyceride (TG) and cholesterol levels, hypertension and risk for cardiovascular disease. The G allele leads to an increased functional enzyme, which is thus associated with decreased levels of TG, VLDL and low-density lipoprotein (LDL) levels compared to the CC genotype. Carriers of the G allele appear to be responsive to dietary factors including control of omega 6 fatty acids and carbohydrate intake.
LPL Gene Detail
LPL encodes the rate limiting enzyme, lipoprotein lipase, which catalyzes the hydrolysis of triglycerides from circulating chylomicrons into free fatty acids and glycerol and VLDL into LDL. It thus plays an important role in lipid clearance from the blood stream, lipid utilization and lipid storage.
It has been established that LPL activity and mass are associated with fluctuation of TG and high-density lipoprotein cholesterol (HDL-C) levels. Variations in this gene have been related to disorders of lipoprotein metabolism and risk for CVD.
LPL 1595C>G (Ser447X)
The common LPL C>G (Ser447X) polymorphism leads to a premature truncation of the protein, which is short of two amino acids, and generates a restriction site for the enzyme. The G allele has been shown to increase LPL enzymatic activity. The increased functional enzyme, due to the G allele, is thus associated with faster lipid clearance in the blood stream, as well as improved lipid utilization. The LPL 447X (G allele) carriers are associated with having lower TG, and higher HDL-C levels and in turn they have reduced risk of CHD.
Important diet-gene interactions for this SNP exist. Carriers of the minor G allele seem to have protection against developing CHD and displayed a lower fasting TG and triglyceride rich lipoproteins-TG concentrations only when their intake of n-6 polyunsaturated fatty acids was low. Interestingly, a recent study found that a diet high in carbohydrate was positively associated with insulin resistance and raised insulin levels, suggesting that a high carbohydrate diet may not be suitable for G allele carriers with metabolic syndrome.
In individuals who carry the LPL CC genotype, it is important to monitor lipogram and blood pressure levels, and include dietary interventions that are targeted at preventing CHD.
Dietary advice for individuals who carry the G allele, include monitoring intake of omega 6 fatty acids, and limiting total carbohydrate intake, especially in those with metabolic syndrome.
Lipoprotein Lipase Gene Sequencing and Plasma Lipid Profile
Pirim et al, 2013.