The Genetic Variations of RETNLB Gene are Associated with Serum Levels of Alkaline Phosphatase in the Korean Population

  • Ahn, Hyo-Jun (Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital) ;
  • Eom, Yong-Bin (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University)
  • 투고 : 2013.12.14
  • 심사 : 2013.12.23
  • 발행 : 2013.12.31

초록

Serum levels of alkaline phosphatase (ALP) are widely used in the clinical diagnosis of hepatic diseases and the assessment of liver status. They also have epidemiological significance to be prospective risk factors for bone diseases, such as osteitis deformans, rickets, osteomalacia, hyperparathyroidism, healing fractures, and osteoblastic bone tumors. In the previous study, single nucleotide polymorphisms (SNPs) in several genes have been reported to be associated with serum levels of liver enzyme in American population. We aimed to confirm whether the genetic variation of RETNLB (resistin like beta) gene also influence the serum levels of liver enzyme in Korean population. We genotyped variants in or near RETNLB in a population-based sample including 994 Korean adults. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in RETNLB gene with serum levels of liver enzyme. By examining genotype data of a total of 944 subjects in 5 hospital health promotion centers, we discovered the RETNLB gene polymorphisms are associated with serum levels of ALP. The common and highest significant polymorphism was rs736327 (${\beta}$=8.66, P=2.37E-05), rs7639070 (${\beta}$=8.56, P=3.24E-05) with ALP in all groups. Furthermore, the ALP was consistently associated with rs736327 (${\beta}$=10.40, P=5.23E-05), rs7639070 (${\beta}$=10.32, P=6.74E-05) in the male population. Consequently, we found statistically significant SNPs in RETNLB gene that are associated with serum levels of ALP. In addition, these results suggest that the individuals with the minor alleles of the SNP in the RETNLB gene may have elevated serum levels of ALP in the Korean population.

키워드

참고문헌

  1. Abraham NZ, Carty RP, DuFour DR, Pincus MR. Clinical enzymology. In: McPherson RA, Pincus MR, eds. Henry's clinical diagnosis and management by laboratory methods. 21st ed. 2007. pp 245-262. Philadelphia: Elsevier Saunders.
  2. Ahn HJ, Sull JW, Eom YB. Association between SMAD2 gene and serum liver enzyme levels in the korean populaton. J Exp Biomed Sci. 2013. 19: 124-131.
  3. Burtis CA, Ashwood ER, Bruns DE, eds. Tietz textbook of clinical chemistry and molecular diagnositcs. 4th ed. 2006. pp 191-218, 597-643. Philadelphia: Elsevier Saunders.
  4. Cereghini S, Yaniv M, Cortese R. Hepatocyte dedifferentiation and extinction is accompanied by a block in the synthesis of mRNA coding for the transcription factor HNF1/LFB1. EMBO J. 1990. 9: 2257-2263.
  5. Christenson RH. Biochemical markers of bone metabolism: an overview. Clin Biochem. 1997. 30: 573-593. https://doi.org/10.1016/S0009-9120(97)00113-6
  6. Foreman JE, Blizard DA, Gerhard G, Mack HA, Lang DH, Van Nimwegen KL, Vogler GP, Stout JT, Shihabi ZK, Griffith JW, Lakoski JM, McClearn GE, Vandenbergh DJ. Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/ 6J and DBA/2J mice. Physiol Genomics. 2005. 23: 295-303. https://doi.org/10.1152/physiolgenomics.00062.2005
  7. Hivert MF, Manning AK, McAteer JB, Dupuis J, Fox CS, Cupples LA, Meigs JB, Florez JC. Association of variants in RETN with plasma resistin levels and diabetes-related traits in the Framingham Offspring Study. Diabetes. 2009. 58: 750-756. https://doi.org/10.2337/db08-1339
  8. Osawa H, Yamada K, Onuma H, Murakami A, Ochi M, Kawata H, Nishimiya T, Niiya T, Shimizu I, Nishid a W, Hashiramoto M, Kanatsuka A, Fujii Y, Ohashi J, Makino H. The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. Am J Hum Genet. 2004. 75: 678-686. https://doi.org/10.1086/424761
  9. Wu AHB. Diagnostic enzymology and other biomarkers of organ damage. In: McClatchery KD, ed. Clinical laboratory medicine. 2nd ed. 2001. pp 281-305. Philadelphia, Lippincott Williams & Wilkins.
  10. Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008. 83: 520-528. https://doi.org/10.1016/j.ajhg.2008.09.012