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. 2022 Aug 22;13(8):1497.
doi: 10.3390/genes13081497.

Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome

Sanghoo Lee  1 , Seol-A Kim  1 , Yejin Kim  1 , Juhoon Kim  1 , Gayeon Hong  1 , Jeonghoon Hong  1 , Kyeonghwan Choi  2 , Chun-Sick Eom  2 , Saeyun Baik  3 , Mi-Kyeong Lee  4 , Kyoung-Ryul Lee  1   2   3   4
Affiliations

Genetic Variants Associated with Elevated Plasma Ceramides in Individuals with Metabolic Syndrome

Sanghoo Lee et al. Genes (Basel). .

Abstract

Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10−2). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10−2. Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS.

Keywords: KoreanChip; SNP genotyping; ceramide species; genetic determinants; metabolic syndrome; plasma ceramide accumulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MRM chromatograms of (A) Cer-16, Cer-18, and Cer-20, and (B) DhCer-16, DhCer-18, DhCer-24, and DhCer-24:1 spiked at 50 ng/mL in 4% BSA with control human plasma. The STD and ISTD indicate the standard and internal standard, respectively. Cer-18-d7 and DhCer-13-d7 were used as ISTDs.
Figure 2
Figure 2
Genes associated with ceramide biosynthesis pathway. Loci in bold are those with variants identified in our study.
Figure 3
Figure 3
A plot of correlation between SNPs and plasma ceramides.
See this image and copyright information in PMC

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