Association of polymorphisms of circadian gene, Clock and Clif, with hyperlipidemia in Chinese Han descent

Abstract

Circadian gene, Clock and Clif, not only maintain the circadian rhythm of cells but also regulate lipid and glucose metabolism in peripheral organs. The purpose of this study was to determine whether genetic variations (single nucleotide polymorphisms – SNPs) in the Clock and/or Clif genes were associated with hyperlipidemia in Chinese Han descent. The Clock variants (rs3840267, rs3749474, rs1052925) and the Clif variant (rs2289709) were analyzed in 205 patients with hyperlipidemia and 281 healthy controls by sequence-specific primer polymerase chain reaction (SSP-PCR). The Clock variant (rs1052925) showed significant association to hyperlipidemia (P _alleo = 0.003, OR_alleo =  0.529). We also found correlations between the Clock (rs1052925), the Clif (rs2289709), and types of hyperlipidemia (P _alleo-IV = 0.043, OR_alleo-IV = 0.525; P _alleo-IIb = 4.738 × 10⁻⁴, OR _alleo-IIb = 2.959). In addition, the Clock (rs1052925), the level of triglycerides in carriers of A/- heterozygote was significantly different from carriers of A/A heterozygote (1.27 ± 0.69 vs. 1.76 ± 1.22; P = 0.01). The Clif (rs2289709), the level of triglycerides and LDL cholesterol in carriers of G/A heterozygote wassignificantly different from carriers of G/G heterozygote (2.31 ± 1.81 vs. 1.11 ± 0.32; P = 2.33 × 10⁻⁸; 2.83 ± 0.98 vs. 1.63 ± 0.69; P = 5.83 × 10⁻¹⁵, respectively). Our findings indicate that Clock/Clif genetic variations might be associated with hyperlipidemia.

Keywords:

• Clock
• Clif
• hyperlipidemia
• polymorphism

Acknowledgments

This research was supported by National Basic Research Program of China (973 Program), No. 2011CB711000 and The Opening Foundation of the State Key Laboratory of Space Medicine Fundamentals and Application, Chinese Astronaut Research and Training Center, Grant No. SMFA09K04.