Advertisement

AGE

, 38:46 | Cite as

Joint effect of gene-physical activity and the interactions among CRP, TNF-α, and LTA polymorphisms on serum CRP, TNF-α levels, and handgrip strength in community-dwelling elders in Taiwan - TCHS-E

  • Chia-Ing Li
  • Tsai-Chung Li
  • Li-Na Liao
  • Chiu-Shong Liu
  • Chuan-Wei Yang
  • Chih-Hsueh Lin
  • Jen-Hao Hsiao
  • Nai-Hsin Meng
  • Wen-Yuan Lin
  • Fang-Yang WuEmail author
  • Cheng-Chieh LinEmail author
Article

Abstract

This study assesses interactions of tumor necrosis factor α (TNF-α) gene polymorphisms with C-reactive protein (CRP) or lymphotoxin α (LTA) gene on serum CRP and TNF-α levels and handgrip strength. Eleven single nucleotide polymorphisms (SNPs), including rs2794520, rs1205, rs1130864, rs1800947, and rs3093059 in CRP; rs1799964, rs1800629, and rs3093662 in TNF-α; and rs2239704, rs909253, and rs1041981 in LTA, were genotyped in 472 unrelated elders (mean age 73.8 years). Among elders with TNF-α rs1799964 AA genotype, adjusted mean difference for handgrip strength decreased by −2.60 (−4.82, −0.38) and −2.51 kg (−4.75, −0.28) for LTA rs909253 and rs1041981 in women and by −2.39 kg (−3.98, −0.81) for CRP rs3093059 in men. Among elders with TNF-α rs1799964 AA genotype, adjusted mean ratios for hs-CRP levels increased by 2.32 (1.38, 3.90) and 2.27 (1.35, 3.84) for both CRP rs909253 and rs1041981 in women. The A-A-C LTA haplotype was associated with TNF-α levels that were 1.55 times higher than those of the C-G-A haplotype (P = 0.005). The joint effects of SNPs (the rs1800947 or rs3093059 of CRP, rs1799964 or rs1800629 of TNF-α, and rs909253 or rs1041981 of LTA) and physical inactivity appeared to have greater magnitude of decreased handgrip strength than main effects of these SNPs and physical inactivity. Our data showed that significant interactions of TNF-αrs1799964 and LTA rs909253 were observed. Moreover, joint effects of these CRP, TNF-α, and LTA risk alleles with physical inactivity in elders were observed, suggesting that physical activity may modulate effects of genotypes on handgrip strength.

Keywords

CRP TNF-α LTA SNP Joint effect Interaction Handgrip strength 

Notes

Acknowledgments

This study was supported by grants from the National Health Research Institutes of Taiwan (NHRI-EX98-9838PI), China Medical University Hospital (DMR-104-067), and the Taiwan Department of Health Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019).

Compliance with ethical standards

Disclosures

The authors have no funding and conflicts of interest to disclose.

References

  1. Abraham LJ, Kroeger KM (1999) Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol 66(4):562–566PubMedGoogle Scholar
  2. Abramson JL, Vaccarino V (2002) Relationship between physical activity and inflammation among apparently healthy middle-aged and older US adults. Arch Intern Med 162(11):1286–1292CrossRefPubMedGoogle Scholar
  3. Arden NK, Spector TD (1997) Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res 12(12):2076–2081. doi: 10.1359/jbmr.1997.12.12.2076 CrossRefPubMedGoogle Scholar
  4. Arking DE, Fallin DM, Fried LP, Li T, Beamer BA, Xue QL, Walston J (2006) Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. J Am Geriatr Soc 54(5):823–826. doi: 10.1111/j.1532-5415.2006.00693.x CrossRefPubMedGoogle Scholar
  5. Ballou SP, Lozanski FB, Hodder S, Rzewnicki DL, Mion LC, Sipe JD, Kushner I (1996) Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons. Age Ageing 25(3):224–230CrossRefPubMedGoogle Scholar
  6. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265. doi: 10.1093/bioinformatics/bth457 CrossRefPubMedGoogle Scholar
  7. Borodulin K, Laatikainen T, Salomaa V, Jousilahti P (2006) Associations of leisure time physical activity, self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults. Atherosclerosis 185(2):381–387. doi: 10.1016/j.atherosclerosis.2005.06.015 CrossRefPubMedGoogle Scholar
  8. Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ, Nicklas BJ (2009) Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci 64(4):455–461. doi: 10.1093/gerona/gln038 CrossRefPubMedGoogle Scholar
  9. Bruunsgaard H (2006) The clinical impact of systemic low-level inflammation in elderly populations. With special reference to cardiovascular disease, dementia and mortality. Dan Med Bull 53(3):285–309PubMedGoogle Scholar
  10. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK (1999) A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 54(7):M357–M364CrossRefPubMedGoogle Scholar
  11. Bruunsgaard H, Benfield TL, Andersen-Ranberg K, Hjelmborg J, Pedersen AN, Schroll M, Jeune B (2004) The tumor necrosis factor alpha -308G > A polymorphism is associated with dementia in the oldest old. J Am Geriatr Soc 52(8):1361–1366. doi: 10.1111/j.1532-5415.2004.52369.x CrossRefPubMedGoogle Scholar
  12. Bruunsgaard H, Pedersen M, Pedersen BK (2001) Aging and proinflammatory cytokines. Curr Opin Hematol 8(3):131–136CrossRefPubMedGoogle Scholar
  13. Carmelli D, Kelly-Hayes M, Wolf PA, Swan GE, Jack LM, Reed T, Guralnik JM (2000) The contribution of genetic influences to measures of lower-extremity function in older male twins. J Gerontol A Biol Sci Med Sci 55(1):B49–B53CrossRefPubMedGoogle Scholar
  14. Carroll MC, Katzman P, Alicot EM, Koller BH, Geraghty DE, Orr HT, Spies T (1987) Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci U S A 84(23):8535–8539CrossRefPubMedPubMedCentralGoogle Scholar
  15. Castro-Giner F, Kogevinas M, Machler M, de Cid R, Van Steen K, Imboden M, Probst-Hensch NM (2008) TNFA -308G > A in two international population-based cohorts and risk of asthma. Eur Respir J 32(2):350–361. doi: 10.1183/09031936.00155607 CrossRefPubMedGoogle Scholar
  16. Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Ferrucci L (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59(3):242–248CrossRefPubMedGoogle Scholar
  17. Colbert LH, Visser M, Simonsick EM, Tracy RP, Newman AB, Kritchevsky SB, Harris TB (2004) Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc 52(7):1098–1104. doi: 10.1111/j.1532-5415.2004.52307.x CrossRefPubMedGoogle Scholar
  18. Coppack SW (2001) Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 60(3):349–356CrossRefPubMedGoogle Scholar
  19. Crawford DC, Sanders CL, Qin X, Smith JD, Shephard C, Wong M, Nickerson DA (2006) Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. Circulation 114(23):2458–2465. doi: 10.1161/CIRCULATIONAHA.106.615740 CrossRefPubMedGoogle Scholar
  20. Dato S, Montesanto A, Lagani V, Jeune B, Christensen K, Passarino G (2012) Frailty phenotypes in the elderly based on cluster analysis: a longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty. Age (Dordr) 34(3):571–582. doi: 10.1007/s11357-011-9257-x CrossRefGoogle Scholar
  21. de Maat MP, Bladbjerg EM, Hjelmborg J, Bathum L, Jespersen J, Christensen K (2004) Genetic influence on inflammation variables in the elderly. Arterioscler Thromb Vasc Biol 24(11):2168–2173. doi: 10.1161/01.ATV.0000143856.01669.e7 CrossRefPubMedGoogle Scholar
  22. Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Paganelli R (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23(9):2375–2378. doi: 10.1002/eji.1830230950 CrossRefPubMedGoogle Scholar
  23. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Longo DL (2005) The origins of age-related proinflammatory state. Blood 105(6):2294–2299. doi: 10.1182/blood-2004-07-2599 CrossRefPubMedGoogle Scholar
  24. Ferrucci L, Penninx BW, Volpato S, Harris TB, Bandeen-Roche K, Balfour J, Md JM (2002) Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc 50(12):1947–1954CrossRefPubMedGoogle Scholar
  25. Floyd-Smith G, Whitehead AS, Colten HR, Francke U (1986) The human C-reactive protein gene (CRP) and serum amyloid P component gene (APCS) are located on the proximal long arm of chromosome 1. Immunogenetics 24(3):171–176PubMedGoogle Scholar
  26. Frederiksen H, Gaist D, Petersen HC, Hjelmborg J, McGue M, Vaupel JW, Christensen K (2002) Hand grip strength: a phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning. Genet Epidemiol 23(2):110–122. doi: 10.1002/gepi.1127 CrossRefPubMedGoogle Scholar
  27. Geffken DF, Cushman M, Burke GL, Polak JF, Sakkinen PA, Tracy RP (2001) Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 153(3):242–250CrossRefPubMedGoogle Scholar
  28. Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, et al. (2003) Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 42(5):861–868CrossRefPubMedGoogle Scholar
  29. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, et al. (1984) Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature 312(5996):721–724CrossRefPubMedGoogle Scholar
  30. Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15(2):475–482. doi: 10.1096/fj.00-0274com CrossRefPubMedGoogle Scholar
  31. Hage FG, Szalai AJ (2007) C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 50(12):1115–1122. doi: 10.1016/j.jacc.2007.06.012 CrossRefPubMedGoogle Scholar
  32. Hajeer AH, Hutchinson IV (2000) TNF-alpha gene polymorphism: clinical and biological implications. Microsc Res Tech 50(3):216–228. doi: 10.1002/1097-0029(20000801)50:3<216::AID-JEMT5>3.0.CO;2-Q CrossRefPubMedGoogle Scholar
  33. Hajeer AH, Hutchinson IV (2001) Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol 62(11):1191–1199CrossRefPubMedGoogle Scholar
  34. Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115(1):1–20. doi: 10.1111/j.1365-2567.2005.02143.x CrossRefPubMedPubMedCentralGoogle Scholar
  35. Hollegaard MV, Bidwell JL (2006) Cytokine gene polymorphism in human disease: on-line databases, Supplement 3. Genes Immun 7(4):269–276. doi: 10.1038/sj.gene.6364301 CrossRefPubMedGoogle Scholar
  36. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMedGoogle Scholar
  37. Huang Y, Yu X, Wang L, Zhou S, Sun J, Feng N, et al. (2013) Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis. PLoS One 8(12):e82519. doi: 10.1371/journal.pone.0082519 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ip EH, Church T, Marshall SA, Zhang Q, Marsh AP, Guralnik J, et al. (2013) Physical activity increases gains in and prevents loss of physical function: results from the lifestyle interventions and independence for elders pilot study. J Gerontol A Biol Sci Med Sci 68(4):426–432. doi: 10.1093/gerona/gls186 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Kardys I, de Maat MP, Uitterlinden AG, Hofman A, Witteman JC (2006) C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study. Eur Heart J 27(11):1331–1337. doi: 10.1093/eurheartj/ehl018 CrossRefPubMedGoogle Scholar
  40. Keso T, Perola M, Laippala P, Ilveskoski E, Kunnas TA, Mikkelsson J, et al. (2001) Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men. Atherosclerosis 154(3):691–697CrossRefPubMedGoogle Scholar
  41. Knight JC, Keating BJ, Kwiatkowski DP (2004) Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1. Nat Genet 36(4):394–399. doi: 10.1038/ng1331 CrossRefPubMedGoogle Scholar
  42. Kohaar I, Tiwari P, Kumar R, Nasare V, Thakur N, Das BC, Bharadwaj M (2009) Association of single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer risk in Indian population. Breast Cancer Res Treat 114(2):347–355. doi: 10.1007/s10549-008-0006-5 CrossRefPubMedGoogle Scholar
  43. Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39(5):687–699. doi: 10.1016/j.exger.2004.01.009 CrossRefPubMedGoogle Scholar
  44. Kritchevsky SB, Cesari M, Pahor M (2005) Inflammatory markers and cardiovascular health in older adults. Cardiovasc Res 66(2):265–275. doi: 10.1016/j.cardiores.2004.12.026 CrossRefPubMedGoogle Scholar
  45. Lin CC, Li CI, Chang CK, Liu CS, Lin CH, Meng NH, Li TC (2011) Reduced health-related quality of life in elders with frailty: a cross-sectional study of community-dwelling elders in Taiwan. PLoS One 6(7):e21841. doi: 10.1371/journal.pone.0021841 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lin CC, Wu FY, Liao LN, Li CI, Lin CH, Yang CW, Li TC (2014) Association of CRP gene polymorphisms with serum CRP level and handgrip strength in community-dwelling elders in Taiwan: Taichung Community Health Study for Elders (TCHS-E). Exp Gerontol 57:141–148. doi: 10.1016/j.exger.2014.05.012 CrossRefPubMedGoogle Scholar
  47. Liu D, Metter EJ, Ferrucci L, Roth SM (2008) TNF promoter polymorphisms associated with muscle phenotypes in humans. J Appl Physiol (1985) 105(3):859–867. doi: 10.1152/japplphysiol.90655.2008 CrossRefGoogle Scholar
  48. Mattusch F, Dufaux B, Heine O, Mertens I, Rost R (2000) Reduction of the plasma concentration of C-reactive protein following nine months of endurance training. Int J Sports Med 21(1):21–24. doi: 10.1055/s-2000-8852 CrossRefPubMedGoogle Scholar
  49. McDevitt H, Munson S, Ettinger R, Wu A (2002) Multiple roles for tumor necrosis factor-alpha and lymphotoxin alpha/beta in immunity and autoimmunity. Arthritis Res 4(Suppl 3):S141–S152CrossRefPubMedPubMedCentralGoogle Scholar
  50. Messer G, Spengler U, Jung MC, Honold G, Blomer K, Pape GR, Weiss EH (1991) Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med 173(1):209–219CrossRefPubMedGoogle Scholar
  51. Miller DT, Zee RY, Suk Danik J, Kozlowski P, Chasman DI, Lazarus R, et al. (2005) Association of common CRP gene variants with CRP levels and cardiovascular events. Ann Hum Genet 69(Pt 6):623–638. doi: 10.1111/j.1529-8817.2005.00210.x CrossRefPubMedGoogle Scholar
  52. Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, et al. (1999) Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA 282(6):561–568CrossRefPubMedGoogle Scholar
  53. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Gray PW (1985) Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res 13(17):6361–6373CrossRefPubMedPubMedCentralGoogle Scholar
  54. Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Tanaka T (2002) Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet 32(4):650–654. doi: 10.1038/ng1047 CrossRefPubMedGoogle Scholar
  55. Pankow JS, Folsom AR, Cushman M, Borecki IB, Hopkins PN, Eckfeldt JH, Tracy RP (2001) Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis 154(3):681–689CrossRefPubMedGoogle Scholar
  56. Petersen AM, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol (1985) 98(4):1154–1162. doi: 10.1152/japplphysiol.00164.2004 CrossRefGoogle Scholar
  57. Peterson PK, Chao CC, Carson P, Hu S, Nichol K, Janoff EN (1994) Levels of tumor necrosis factor alpha, interleukin 6, interleukin 10, and transforming growth factor beta are normal in the serum of the healthy elderly. Clin Infect Dis 19(6):1158–1159CrossRefPubMedGoogle Scholar
  58. Pociot F, Briant L, Jongeneel CV, Molvig J, Worsaae H, Abbal M, Cambon-Thomsen A (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23(1):224–231. doi: 10.1002/eji.1830230135 CrossRefPubMedGoogle Scholar
  59. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi: 10.1086/519795 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Qidwai T, Khan F (2011) Tumour necrosis factor gene polymorphism and disease prevalence. Scand J Immunol 74(6):522–547. doi: 10.1111/j.1365-3083.2011.02602.x CrossRefPubMedGoogle Scholar
  61. Rantanen T, Guralnik JM, Foley D, Masaki K, Leveille S, Curb JD, White L (1999) Midlife hand grip strength as a predictor of old age disability. JAMA 281(6):558–560CrossRefPubMedGoogle Scholar
  62. Richards CD, Gauldie J (1995) Role of cytokines in the acute-phase response. In: Aggarwal BB, Puri RK (eds) Human Cytokines: Their Roles in Disease and Therapy. Blackwell Science, Cambridge, MA, pp. 253–269Google Scholar
  63. Santos ML, Gomes WF, Pereira DS, Oliveira DM, Dias JM, Ferrioli E, Pereira LS (2011) Muscle strength, muscle balance, physical function and plasma interleukin-6 (IL-6) levels in elderly women with knee osteoarthritis (OA). Arch Gerontol Geriatr 52(3):322–326. doi: 10.1016/j.archger.2010.05.009 CrossRefPubMedGoogle Scholar
  64. Schaap LA, Pluijm SM, Deeg DJ, Harris TB, Kritchevsky SB, Newman AB, Health ABCS (2009) Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci 64(11):1183–1189. doi: 10.1093/gerona/glp097 CrossRefPubMedGoogle Scholar
  65. Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76(6):959–962CrossRefPubMedGoogle Scholar
  66. Su KP (2012) Inflammation in psychopathology of depression: clinical, biological, and therapeutic implications. Biomedicine 2(2):68–74CrossRefGoogle Scholar
  67. Tan JH, Temple SE, Kee C, Waterer GW, Tan CR, Gut I, Price P (2011) Characterisation of TNF block haplotypes affecting the production of TNF and LTA. Tissue Antigens 77(2):100–106. doi: 10.1111/j.1399-0039.2010.01582.x CrossRefPubMedGoogle Scholar
  68. Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylha M (2010) Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci 65(6):658–663. doi: 10.1093/gerona/glq056 CrossRefPubMedGoogle Scholar
  69. Tikkanen P, Nykanen I, Lonnroos E, Sipila S, Sulkava R, Hartikainen S (2012) Physical activity at age of 20-64 years and mobility and muscle strength in old age: a community-based study. J Gerontol A Biol Sci Med Sci 67(8):905–910. doi: 10.1093/gerona/gls005 CrossRefPubMedGoogle Scholar
  70. Udalova IA, Nedospasov SA, Webb GC, Chaplin DD, Turetskaya RL (1993) Highly informative typing of the human TNF locus using six adjacent polymorphic markers. Genomics 16(1):180–186. doi: 10.1006/geno.1993.1156 CrossRefPubMedGoogle Scholar
  71. Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Harris TB (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57(5):M326–M332CrossRefPubMedGoogle Scholar
  72. Walsh MT, Divane A, Whitehead AS (1996) Fine mapping of the human pentraxin gene region on chromosome 1q23. Immunogenetics 44(1):62–69CrossRefPubMedGoogle Scholar
  73. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A 94(7):3195–3199CrossRefPubMedPubMedCentralGoogle Scholar
  74. Zeggini E, Groves CJ, Parkinson JR, Halford S, Owen KR, Frayling TM, McCarthy MI (2005) Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. Diabetologia 48(10):2013–2017. doi: 10.1007/s00125-005-1902-4 CrossRefPubMedGoogle Scholar

Copyright information

© American Aging Association 2016

Authors and Affiliations

  • Chia-Ing Li
    • 1
  • Tsai-Chung Li
    • 3
    • 4
  • Li-Na Liao
    • 1
  • Chiu-Shong Liu
    • 1
    • 5
  • Chuan-Wei Yang
    • 2
    • 6
  • Chih-Hsueh Lin
    • 1
    • 5
  • Jen-Hao Hsiao
    • 7
  • Nai-Hsin Meng
    • 1
    • 8
  • Wen-Yuan Lin
    • 1
    • 5
  • Fang-Yang Wu
    • 9
    Email author
  • Cheng-Chieh Lin
    • 1
    • 5
    Email author
  1. 1.School of Medicine, College of MedicineChina Medical UniversityTaichungTaiwan
  2. 2.Department of Medical ResearchChina Medical University HospitalTaichungTaiwan
  3. 3.Graduate Institute of Biostatistics, College of Public HealthChina Medical UniversityTaichungTaiwan
  4. 4.Department of Healthcare Administration, College of Medical and Health SciencesAsia UniversityTaichungTaiwan
  5. 5.Department of Family MedicineChina Medical University HospitalTaichungTaiwan
  6. 6.Ph.D. Program for Aging, College of MedicineChina Medical UniversityTaichungTaiwan
  7. 7.Bioinformatics and Biostatistics Core, Center of Genomic MedicineNational Taiwan UniversityTaipeiTaiwan
  8. 8.Department of Physical Medicine and RehabilitationChina Medical University HospitalTaichungTaiwan
  9. 9.Department of Public Health, College of Public HealthChina Medical UniversityTaichungTaiwan

Personalised recommendations