Advertisement

Human Genetics

, Volume 127, Issue 6, pp 685–690 | Cite as

A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle

  • Kazuhiro Nakayama
  • Tumenbayer Bayasgalan
  • Fumiko Tazoe
  • Yoshiko Yanagisawa
  • Takaya Gotoh
  • Kazuhiro Yamanaka
  • Ayumi Ogawa
  • Lkhagvasuren Munkhtulga
  • Ulziiburen Chimedregze
  • Yasuo Kagawa
  • Shun Ishibashi
  • Sadahiko IwamotoEmail author
  • Jichi Medical University Promotion Team of a Large-scale Human Genome Bank for All over Japan
Original Investigation

Abstract

Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype–phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 × 10−6) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 × 10−6), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.

Keywords

Multiple Linear Regression Model European Ancestry Plasma Lipid Profile Plasma Lipid Concentration Similar Genetic Background 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This study was supported in part by Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare, and by a Grant-in-Aid for Young Scientists (B) 19770214 and (A) 21687021. This publication was subsidized by JKA through its promotion founds from KEIRIN RACE.

References

  1. Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, Penninx BW, Janssens AC, Wilson JF, Spector T, Martin NG, Pedersen NL, Kyvik KO, Kaprio J, Hofman A, Freimer NB, Jarvelin MR, Gyllensten U, Campbell H, Rudan I, Johansson A, Marroni F, Hayward C, Vitart V, Jonasson I, Pattaro C, Wright A, Hastie N, Pichler I, Hicks AA, Falchi M, Willemsen G, Hottenga JJ, de Geus EJ, Montgomery GW, Whitfield J, Magnusson P, Saharinen J, Perola M, Silander K, Isaacs A, Sijbrands EJ, Uitterlinden AG, Witteman JC, Oostra BA, Elliott P, Ruokonen A, Sabatti C, Gieger C, Meitinger T, Kronenberg F, Doring A, Wichmann HE, Smit JH, McCarthy MI, van Duijn CM, Peltonen L (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 41:47–55CrossRefPubMedGoogle Scholar
  2. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265CrossRefPubMedGoogle Scholar
  3. Hartweg J, Farmer AJ, Perera R, Holman RR, Neil HA (2007) Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia 50:1593–1602CrossRefPubMedGoogle Scholar
  4. Jacobson TA (2008) Role of n-3 fatty acids in the treatment of hypertriglyceridemia and cardiovascular disease. Am J Clin Nutr 87:1981S–1990SPubMedGoogle Scholar
  5. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS, Wahlstrand B, Hedner T, Corella D, Tai ES, Ordovas JM, Berglund G, Vartiainen E, Jousilahti P, Hedblad B, Taskinen MR, Newton-Cheh C, Salomaa V, Peltonen L, Groop L, Altshuler DM, Orho-Melander M (2008) Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 40:189–197CrossRefPubMedGoogle Scholar
  6. Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, Kaplan L, Bennett D, Li Y, Tanaka T, Voight BF, Bonnycastle LL, Jackson AU, Crawford G, Surti A, Guiducci C, Burtt NP, Parish S, Clarke R, Zelenika D, Kubalanza KA, Morken MA, Scott LJ, Stringham HM, Galan P, Swift AJ, Kuusisto J, Bergman RN, Sundvall J, Laakso M, Ferrucci L, Scheet P, Sanna S, Uda M, Yang Q, Lunetta KL, Dupuis J, de Bakker PI, O’Donnell CJ, Chambers JC, Kooner JS, Hercberg S, Meneton P, Lakatta EG, Scuteri A, Schlessinger D, Tuomilehto J, Collins FS, Groop L, Altshuler D, Collins R, Lathrop GM, Melander O, Salomaa V, Peltonen L, Orho-Melander M, Ordovas JM, Boehnke M, Abecasis GR, Mohlke KL, Cupples LA (2009) Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 41:56–65CrossRefPubMedGoogle Scholar
  7. Komatsu F, Kagawa Y, Sakuma M, Kawabata T, Kaneko Y, Otgontuya D, Chimedregzen U, Narantuya L, Purvee B (2006) Investigation of oxidative stress and dietary habits in Mongolian people, compared to Japanese people. Nutr Metab 3:21CrossRefGoogle Scholar
  8. Kooner JS, Chambers JC, Aguilar-Salinas CA, Hinds DA, Hyde CL, Warnes GR, Gomez Perez FJ, Frazer KA, Elliott P, Scott J, Milos PM, Cox DR, Thompson JF (2008) Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nat Genet 40:149–151CrossRefPubMedGoogle Scholar
  9. Liew M, Pryor R, Palais R, Meadows C, Erali M, Lyon E, Wittwer C (2004) Genotyping of single-nucleotide polymorphisms by high-resolution melting of small amplicons. Clin Chem 50:1156–1164CrossRefPubMedGoogle Scholar
  10. Marquardt A, Stohr H, White K, Weber BH (2000) cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics 66:175–183CrossRefPubMedGoogle Scholar
  11. Munkhtulga L, Nakayama K, Utsumi N, Yanagisawa Y, Gotoh T, Omi T, Kumada M, Erdenebulgan B, Zolzaya K, Lkhagvasuren T, Iwamoto S (2007) Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia. Hum Genet 120:879–888CrossRefPubMedGoogle Scholar
  12. Nakayama K, Lkhagvasuren M, Yanagisawa Y, Utsumi N, Kumada M, Gotoh T, Iwamoto S, Kagawa Y (2008) Comparative study of polymorphisms on genes associated with lifestyle related diseases in Asian and Pacific populations. Asia Pac J Public Health 20(Suppl):173–179Google Scholar
  13. Nakayama K, Bayasgalan T, Yamanaka K, Kumada M, Gotoh T, Utsumi N, Yanagisawa Y, Okayama M, Kajii E, Ishibashi S, Iwamoto S, Jichi Community Genetics Team (JCOG) (2009) Large scale replication analysis of loci associated with lipid concentrations in a Japanese population. J Med Genet 46:370–374CrossRefPubMedGoogle Scholar
  14. Nogi A, Yang J, Li L, Yamasaki M, Watanabe M, Hashimoto M, Shiwaku K (2007) Plasma n-3 polyunsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean and Mongolian workers. J Occup Health 49:205–216CrossRefPubMedGoogle Scholar
  15. Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, Jones CG, Zaitlen NA, Varilo T, Kaakinen M, Sovio U, Ruokonen A, Laitinen J, Jakkula E, Coin L, Hoggart C, Collins A, Turunen H, Gabriel S, Elliot P, McCarthy MI, Daly MJ, Jarvelin MR, Freimer NB, Peltonen L (2009) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 41:35–46CrossRefPubMedGoogle Scholar
  16. Schaeffer L, Gohlke H, Muller M, Heid IM, Palmer LJ, Kompauer I, Demmelmair H, Illig T, Koletzko B, Heinrich J (2006) Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 15:1745–1756CrossRefPubMedGoogle Scholar
  17. Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, Guralnik JM, Singleton A, Bandinelli S, Cherubini A, Arnett D, Tsai MY, Ferrucci L (2009) Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet 5:e1000338CrossRefPubMedGoogle Scholar
  18. Wijendran V, Hayes KC (2004) Dietary n-6 and n-3 fatty acid balance and cardiovascular health. Annu Rev Nutr 24:597–615CrossRefPubMedGoogle Scholar
  19. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Shlomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40:161–169CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kazuhiro Nakayama
    • 1
  • Tumenbayer Bayasgalan
    • 2
  • Fumiko Tazoe
    • 2
  • Yoshiko Yanagisawa
    • 1
  • Takaya Gotoh
    • 1
  • Kazuhiro Yamanaka
    • 1
  • Ayumi Ogawa
    • 1
  • Lkhagvasuren Munkhtulga
    • 3
  • Ulziiburen Chimedregze
    • 4
  • Yasuo Kagawa
    • 5
  • Shun Ishibashi
    • 2
  • Sadahiko Iwamoto
    • 1
    Email author
  • Jichi Medical University Promotion Team of a Large-scale Human Genome Bank for All over Japan
    • 6
  1. 1.Division of Human GeneticsCenter for Community Medicine, Jichi Medical UniversityShimotsukeJapan
  2. 2.Division of Endocrinology and Metabolism, Department of Internal MedicineJichi Medical UniversityShimotsukeJapan
  3. 3.Health Science University of MongoliaUlaanbaatarMongolia
  4. 4.Public Health InstituteUlaanbaatarMongolia
  5. 5.Kagawa Nutrition UniversitySakadoJapan
  6. 6.Division of Community and Family MedicineCenter for Community Medicine, Jichi Medical UniversityShimotsukeJapan

Personalised recommendations