High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population

Background Single nucleotide polymorphisms (SNPs) in lipoprotein lipase gene (LPL) have been shown to influence metabolism related to lipid phenotypes. Dietary factors have been shown to modify the association between LPL SNPs and lipids; however, to date, there are no studies in South Asians. Hence, we tested for the association of four common LPL SNPs with plasma lipids and examined the interactions between the SNPs and dietary factors on lipids in 1,845 Asian Indians. Methods The analysis was performed in 788 Type 2 diabetes cases and 1,057 controls randomly chosen from the cross-sectional Chennai Urban Rural Epidemiological Study. Serum triacylglycerol (TAG), serum total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The SNPs (rs1121923, rs328, rs4922115 and rs285) were genotyped by polymerase chain reaction followed by restriction enzyme digestion and 20% of samples were sequenced to validate the genotypes obtained. Statistical Package for Social Sciences for Windows version 22.0 (SPSS, Chicago, IL) was used for statistical analysis. Results After correction for multiple testing and adjusting for potential confounders, SNPs rs328 and rs285 showed association with HDL-C (P = 0.0004) and serum TAG (P = 1×10−5), respectively. The interaction between SNP rs1121923 and fat intake (energy %) on HDL-C (P = 0.003) was also significant, where, among those who consumed a high fat diet (28.4 ± 2.5%), the T allele carriers (TT + XT) had significantly higher HDL-C concentrations (P = 0.0002) and 30% reduced risk of low HDL-C levels compared to the CC homozygotes. None of the interactions on other lipid traits were statistically significant. Conclusion Our findings suggest that individuals carrying T allele of the SNP rs1121923 have increased HDL-C levels when consuming a high fat diet compared to CC homozygotes. Our finding warrants confirmation in prospective studies and randomized controlled trials

The common biological basis for common complex diseases: evidence from lipoprotein lipase gene

The lipoprotein lipase (LPL) gene encodes a rate-limiting enzyme protein that has a key role in the hydrolysis of triglycerides. Hypertriglyceridemia, one widely prevalent syndrome of LPL deficiency and dysfunction, may be a risk factor in the development of dyslipidemia, type II diabetes (T2D), essential hypertension (EH), coronary heart disease (CHD) and Alzheimer's disease (AD). Findings from earlier studies indicate that LPL may have a role in the pathology of these diseases and therefore is a common or shared biological basis for these common complex diseases. To examine this hypothesis, we reviewed articles on the molecular structure, expression and function of the LPL gene, and its potential role in the etiology of diseases. Evidence from these studies indicate that LPL dysfunction is involved in dyslipidemia, T2D, EH, CHD and AD; and support the hypothesis that there is a common or shared biological basis for these common complex diseases