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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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12986-016-0155-1) contains supplementary material, which is available to authorized users.

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