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Plasticity of the Human Plasma Lipidome is Genetically Influenced and Associated with Type 2 Diabetes in Mexican American Families
Author(s) -
Kulkarni Hemant,
Meikle Peter,
Mamtani Manju,
Wong Gerard,
Weir Jacquelyn,
Barlow Christopher,
Dyer Thomas,
Almasy Laura,
Mahaney Michael,
Comuzzie Anthony,
Duggirala Ravindranath,
Blangero John,
Curran Joanne
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.715.5
Subject(s) - lipidome , ceramide , lipidomics , sphingomyelin , type 2 diabetes , population , chemistry , biology , endocrinology , medicine , diabetes mellitus , biochemistry , cholesterol , apoptosis , environmental health
Using Shannon's entropy, we quantified the plasticity of the human plasma lipidome (defined as the extent to which the lipidome departs froma homeostatic equilibrium). Our objective was to test whether a) the plasticity is genetically influenced and b) whether it is associated with the presence of type 2 diabetes (T2D) in the high‐risk population of Mexican Americans. We used data from 1,212 pedigreed individuals (representing 40 large and extended families) recruited in the San Antonio Family Heart Study. The plasma lipidome (318 lipid species, 22 classes) was measured using a combination of high‐performance liquid chromatography and mass spectrometry. Using SOLAR software package and accounting for the kinship structure, we made three interesting observations:Lipid class Mean Entropy SD Entropy h 2 r p(h 2 r) ß (T2D) p(T2D)Dihydroceramide 2.34 0.09 0.28 1.87x10 ‐11 0.03 0.6033 Ceramide 1.96 0.11 0.41 1.98x10 ‐21 0.09 0.0972 Monohexosylceramide 2.12 0.05 0.32 3.27x10 ‐10 0.07 0.2094 Dihexosylceramide 1.43 0.13 0.42 9.95x10 ‐16 0.28 9.93x10 ‐7Trihexosylceramide 1.96 0.10 0.42 1.21x10 ‐18 0.08 0.1638 G M3 ganglioside 2.45 0.04 0.35 3.13x10 ‐12 0.09 0.0948 Sphingomyelin 1.48 0.11 0.53 8.89x10 ‐31 0.06 0.3286 Phosphatidylcholine 3.64 0.12 0.60 2.60x10 ‐30 ‐0.01 0.8930 Alkylphosphatidylcholine 2.83 0.11 0.43 1.26x10 ‐18 0.16 0.0041 Alkenylphosphatidylcholine 1.83 0.17 0.45 4.91x10 ‐27 0.23 3.76x10 ‐5Lysophosphatidylcholine 3.44 0.17 0.31 6.82x10 ‐10 ‐0.17 0.0053 Lysoalkylphosphaidylcholine 1.88 0.11 0.18 0.0001 0.02 0.7757 Phosphatidylethanolamine 2.02 0.09 0.36 2.62x10 ‐12 ‐0.06 0.2637 Alkylphosphatidylethanolamine 2.98 0.14 0.15 0.0001 ‐0.26 1.88x10 ‐6Alkenylphosphatidylethanolamine 2.58 0.09 0.35 6.3x10 ‐15 0.07 0.2354 Lysophosphatidylethanolamine 1.73 0.10 0.27 7.11x10 ‐8 ‐0.17 0.0018Phosphatidylinositol 3.60 0.12 0.41 1.41x10 ‐16 ‐0.06 0.2700 Phosphatidylserine 1.97 0.28 0.42 3.10x10 ‐16 ‐0.28 4.95x10 ‐6Phosphatidylglycerol 1.59 0.10 0.32 1.49x10 ‐9 0.02 0.6771 Cholesteryl ester 2.94 0.16 0.19 1.78x10 ‐5 ‐0.07 0.1684 Diacylglycerol 2.74 0.11 0.37 2.04x10 ‐15 0.11 0.0356 Triacylglycerol 3.76 0.27 0.14 0.0008 0.16 0.0037 Overall 4.83 0.13 0.17 0.0002 ‐0.06 0.2563I) The class‐specific entropy varied widely across classes. II) All entropies were significantly heritable ranging from 0.14 (for triacylglycerols) to 0.60 (for phosphatidylcholines). III) High entropy of the five lipid classes was significantly and independently associated with T2D even after correcting for multiple testing. Our results demonstrate a strong genetic influence on the plasticity of the plasma lipidome and provide novel mechanistic insights by implicating the plasticity of five lipid classes in the pathogenesis of T2D.
This work was supported in part by NIH grants, AT&T Foundation and facilities supported by NIH grants.