(Basel, Switzerland) for supplying PKF115-584. We thank Dr. Manuela Gariboldi (IFOM, Milan, Italy) for providing the SW837 cell line. Funding Statement This work was supported by the Italian Association for Cancer Research (AIRC), Cariplo Foundation, the click here Italian Ministry of Health and Lombardy Regional Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Dyslipidemia, with low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), is a well established risk factor for coronary artery disease (CAD) and a significant cause of mortality in individuals with type 2 diabetes (T2D) [1].
The risk of developing CAD is 2�C3 times higher in diabetic males and 4�C5 times higher in diabetic females compared to male and female non-diabetics [2]. There is considerable ethnic difference in the prevalence and progression of T2D and CAD; the incidences of these diseases are about 3�C5 times higher in Asian Indians compared to Euro-Caucasians [3]. Lipid levels are widely measured in clinical practice and are used as therapeutic targets for prevention and treatment of CAD especially in patients with diabetes [4]. Recent genome-wide association scans (GWAS) and meta-analysis studies in European populations have identified common variants in many genes, including previously known loci that are potentially involved in lipid regulation [5]�C[8].
High heritability (40% to 60%) of lipid traits and strong association signals among common variants in these genes involved in lipid metabolism provide a strong rationale to search for causal variants that may uncover novel pathways crucial for lipid regulation and eventually lead to treatment or prevention of CAD [9], [10]. Replication of GWAS signals in different ethnic groups is important as the frequency of the susceptible alleles at these loci may vary significantly between world populations [11]. Also, these studies can help identify population-specific environmental factors controlling disease risk or protection associated with specific demographic and cultural histories [11]. In particular, replication of GWAS loci associations will have more relevance in population groups with high disease burdens such as Asian Indians [12].
A few studies have reported associations of these novel loci with lipid traits in Asian Indian immigrants living in the UK [6], [13], [14]. The present investigation was carried out to examine the role of six of the most strongly associated and extensively replicated GWAS loci (CELSR2-PSRC1-SORT1 AV-951 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) (summarized in Table 1) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) [15].