Genetic and environmental determinants of population variation in interleukin-6, its soluble receptor and C-reactive protein: Insights from identical and fraternal twins

Brain, Behavior, and Immunity

Volumn 49, Issue , 2015, Pages 171-181

  Amaral, Wellington Z ^a   Krueger, Robert F ^b   Ryff, Carol D ^a   Coe, Christopher L ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

C reactive protein; Heritability; Interleukin 6; Obesity; Soluble interleukin 6 receptor; Twins

Indexed keywords

C REACTIVE PROTEIN; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR;

ADULT; AGE DISTRIBUTION; ARTICLE; BODY MASS; DISEASE MARKER; DIZYGOTIC TWINS; FEMALE; GENDER; HERITABILITY; HUMAN; MALE; MONOZYGOTIC TWINS; OBESITY; PHENOTYPE; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SMOKING; SOCIAL STATUS; CAUCASIAN; ETHNOLOGY; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; MIDDLE AGED; TWINS; UNITED STATES;

BODY MASS INDEX; C-REACTIVE PROTEIN; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENE-ENVIRONMENT INTERACTION; HUMANS; INTERLEUKIN-6; MALE; MIDDLE AGED; OBESITY; RECEPTORS, INTERLEUKIN-6; TWINS; UNITED STATES;

EID: 84940598253     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2015.05.010     Document Type: Article

References (119)

1. Agrawal S., Gollapudi S., Su H., Gupta S. Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J. Clin. Immunol. 2011, 31:472-478.
2. Anty R., Bekri S., Luciani N., Saint-Paul M.-C., Dahman M., Iannelli A., Amor I.Ben, Staccini-Myx A., Huet P.-M., Gugenheim J., Sadoul J.-L., Le Marchand-Brustel Y., Tran A., Gual P. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am. J. Gastroenterol. 2006, 101:1824-1833.
3. Bagli M., Papassotiropoulos A., Hampel H., Becker K., Jessen F., Bürger K., Ptok U., Rao M.L., Möller H.-J., Maier W., Heun R. Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study. Eur. Arch. Psychiatry Clin. Neurosci. 2003, 253:44-48.
4. Behrendt P., Buchenauer T., Horn R., Brabant G., Jacobs R., Bode F., Stephan M., Nave H. Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats. Endocrine 2010, 38:104-112.
5. Bennermo M., Held C., Stemme S., Ericsson C.-G., Silveira A., Green F., Tornvall P. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases?. Clin. Chem. 2004, 50:2136-2140.
6. Bob P., Raboch J., Maes M., Susta M., Pavlat J., Jasova D., Vevera J., Uhrova J., Benakova H., Zima T. Depression, traumatic stress and interleukin-6. J. Affect. Disord. 2010, 120:231-234.
7. Boomsma D., Busjahn A., Peltonen L. Classical twin studies and beyond. Nat. Rev. Genet. 2002, 3:872-882.
8. Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A., Lowe G.D.O., Humphries S.E. Interleukin-6 gene -174G C and -572G C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler. Thromb. Vasc. Biol. 2001, 21:1458-1463.
9. Bruunsgaard H., Christiansen L., Pedersen A.N., Schroll M., Jørgensen T., Pedersen B.K. The IL-6 -174G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans. Exp. Gerontol. 2004, 39:255-261.
10. Burton M.D., Sparkman N.L., Johnson R.W. Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior. J. Neuroinflammation 2011, 8:54.
11. Burzotta F., Iacoviello L., Di Castelnuovo A., Glieca F., Luciani N., Zamparelli R., Schiavello R., Donati M.B., Maseri A., Possati G., Andreotti F. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am. J. Cardiol. 2001, 88:1125-1128.
12. Calabro P., Chang D.W., Willerson J.T., Yeh E.T.H. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. J. Am. Coll. Cardiol. 2005, 46:1112-1113.
13. Carroll J.F., Fulda K.G., Chiapa A.L., Rodriquez M., Phelps D.R., Cardarelli K.M., Vishwanatha J.K., Cardarelli R. Impact of race/ethnicity on the relationship between visceral fat and inflammatory biomarkers. Obesity (Silver Spring) 2009, 17:1420-1427.
14. Chatzikyriakidou A., Voulgari P.V., Lambropoulos A., Drosos A.A. Genetics in rheumatoid arthritis beyond HLA genes: what meta-analyses have shown?. Semin. Arthritis Rheum. 2013, 43(1):29-38.
15. Chen S., Chen T., Lai L., Chen J. Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer's disease. J. Neuroinflammation 2012, 9:21.
16. Christensen K., Støvring H., McGue M. Do genetic factors contribute to the association between birth weight and blood pressure?. J. Epidemiol. Community Health 2001, 55:583-587.
17. Clifton P.M. Diet and C-reactive protein. Curr. Atheroscler. Rep. 2003, 5:431-436.
18. Coe C.L., Love G.D., Karasawa M., Kawakami N., Kitayama S., Markus H.R., Tracy R.P., Ryff C.D. Population differences in proinflammatory biology: Japanese have healthier profiles than Americans. Brain Behav. Immun. 2011, 25:494-502.
19. Coppack S.W. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr. Soc. 2007, 60:349-356.
20. Crawford D.C., Yi Q., Smith J.D., Shephard C., Wong M., Witrak L., Livingston R.J., Rieder M.J., Nickerson D.A. Allelic spectrum of the natural variation in CRP. Hum. Genet. 2006, 119:496-504.
21. Crichton M.B., Nichols J.E., Zhao Y., Bulun S.E., Simpson E.R. Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells. Mol. Cell. Endocrinol. 1996, 118:215-220.
22. Dai L., Liu D., Guo H., Wang Y., Bai Y. Association between polymorphism in the promoter region of Interleukin 6 (-174 G/C) and risk of Alzheimer's disease: a meta-analysis. J. Neurol. 2012, 259:414-419.
23. De Craen A.J.M., Posthuma D., Remarque E.J., van den Biggelaar A.H.J., Westendorp R.G.J., Boomsma D.I. Heritability estimates of innate immunity: an extended twin study. Genes Immun. 2005, 6:167-170.
24. De Maat M.P.M., Bladbjerg E.M., Hjelmborg J.V.B., Bathum L., Jespersen J., Christensen K. Genetic influence on inflammation variables in the elderly. Arterioscler. Thromb. Vasc. Biol. 2004, 24:2168-2173.
25. Dehghan A., Dupuis J., Barbalic M., Bis J.C., Eiriksdottir G., Lu C., et al. Meta-analysis of genome-wide association studies in 80,000 subjects identifies multiple loci for C-reactive protein levels. Circulation 2011, 123:731-738.
26. Di Bona D., Vasto S., Capurso C., Christiansen L., Deiana L., Franceschi C., Hurme M., Mocchegiani E., Rea M., Lio D., Candore G., Caruso C. Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res. Rev. 2009, 8:36-42.
27. Duffy D.L., Mitchell C.A., Martin N.G. Genetic and environmental risk factors for asthma: a cotwin-control study. Am. J. Respir. Crit. Care Med. 1998, 157:840-845.
28. Ershler W., Keller E. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu. Rev. Med. 2000, 245-270.
29. Ferreira R.C., Freitag D.F., Cutler A.J., Howson J.M.M., Rainbow D.B., Smyth D.J., Kaptoge S., Clarke P., Boreham C., Coulson R.M., Pekalski M.L., Chen W.-M., Onengut-Gumuscu S., Rich S.S., Butterworth A.S., Malarstig A., Danesh J., Todd J.A. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet. 2013, 9:e1003444. 10.1371/journal.pgen.1003444.
30. Fried S.K., Bunkin D.A., Greenberg A.S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 1998, 83:847-850.
31. Friedman E.M., Hayney M.S., Love G.D., Urry H.L., Rosenkranz M.A., Rosenkranz M.A., Davidson R.J., Singer B.H., Ryff C.D. Social relationships, sleep quality, and interleukin-6 in aging women. Proc. Natl. Acad. Sci. USA 2005, 102:18757-18762.
32. Galicia J.C., Tai H., Komatsu Y., Shimada Y., Akazawa K., Yoshie H. Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun. 2004, 5:513-516.
33. Gupta N.K., De Lemos J.A., Ayers C.R., Abdullah S.M., McGuire D.K., Khera A. The relationship between C-reactive protein and atherosclerosis differs on the basis of body mass index: the Dallas Heart study. J. Am. Coll. Cardiol. 2012, 60:1148-1155.
34. Hall J.G. Twinning. Lancet 2003, 362:735-743.
35. Hamid Y.H., Urhammer S.A., Jensen D.P., Glümer C., Borch-Johnsen K., Jørgensen T., Hansen T., Pedersen O. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites. Diabetes 2004, 53:3342-3345.
36. Hamzic N., Tang Y., Eskilsson A., Kugelberg U., Ruud J., Jönsson J.-I., Blomqvist A., Nilsberth C. Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response. Brain Behav. Immun. 2013, 33:123-130.
37. Hauser R., Warren J. Socioeconomic Indexes for occupations: a review, update, and critique. Sociol. Methodol. 1997, 27:177-298.
38. Hawkins D. Using U statistics to derive the asymptotic distribution of Fisher's Z statistic. Am. Stat. 1989, 43:235-237.
39. Heinrich P.C., Castell J.V., Andus T. Interleukin-6 and the acute phase response. Biochem. J. 1990, 265:621-636.
40. Herbert A., Liu C., Karamohamed S., Liu J. BMI modifies associations of IL-6 genotypes with insulin resistance: the Framingham study. Obesity 2006, 14:1454-1461.
41. Hjelmborg J.V.B., Fagnani C., Silventoinen K., McGue M., Korkeila M., Christensen K., Rissanen A., Kaprio J. Genetic influences on growth traits of BMI: a longitudinal study of adult twins. Obesity 2008, 16:847-852.
42. Holmes M.V., Lange L.A., Palmer T., Lanktree M.B., North K.E., Almoguera B., et al. Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis. Am. J. Hum. Genet. 2014, 94:198-208.
43. Hotelling H. New light on the correlation coefficient and its transforms. J. R. Stat. Soc. Ser. B Methodol. 1953, 15:193-232.
44. Hurst S.M., Wilkinson T.S., McLoughlin R.M., Jones S., Horiuchi S., Yamamoto N., Rose-John S., Fuller G.M., Topley N., Jones S.A. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 2001, 14:705-714.
45. Huth C., Heid I.M., Vollmert C., Gieger C., Grallert H., Wolford J.K., et al. IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes 2006, 55:2915-2921.
46. Johnson W., Krueger R.F. Genetic effects on physical health: lower at higher income levels. Behav. Genet. 2005, 35:579-590.
47. Jones S.A., Horiuchi S., Topley N., Yamamoto N., Fuller G.M. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001, 15:43-58.
48. Kallen K.-J. The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases. Biochim. Biophys. Acta 2002, 1592:323-343.
49. Karmakar B., Malkin I., Kobyliansky E. Inheritance of dermatoglyphic traits in twins: univariate and bivariate variance decomposition analysis. Anthropol. Anzeiger. 2012, 69:221-228.
50. Khaodhiar L., Ling P.-R., Blackburn G.L., Bistrian B.R. Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity. J. Parenter. Enter. Nutr. 2004, 28:410-415.
51. Kiecolt-Glaser J.K., Preacher K.J., MacCallum R.C., Atkinson C., Malarkey W.B., Glaser R. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc. Natl. Acad. Sci. USA 2003, 100:9090-9095.
52. Kredel L.I., Batra A., Stroh T., Kühl A.A., Zeitz M., Erben U., Siegmund B. Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's Disease. Gut 2013, 62:852-862.
53. Krupp M., Lane M.D. On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell. J. Biol. Chem. 1981, 256:1689-1694.
54. Lamas J.R., Rodríguez-Rodríguez L., Tornero-Esteban P., Villafuertes E., Hoyas J., Abasolo L., Varadé J., Alvarez-Lafuente R., Urcelay E., Fernández-Gutiérrez B. Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis. Cytokine 2013, 61:720-723.
55. Lee Y.H., Bae S.-C., Choi S.J., Ji J.D., Song G.G. The association between interleukin-6 polymorphisms and rheumatoid arthritis: a meta-analysis. Inflamm. Res. 2012, 61:665-671.
56. Lepiller Q., Abbas W., Kumar A., Tripathy M.K., Herbein G. HCMV activates the IL-6-JAK-STAT3 axis in HepG2 cells and primary human hepatocytes. PLoS One 2013, 8:e59591. 10.1371/journal.pone.0059591.
57. Lieb W., Pavlik R., Erdmann J., Mayer B., Holmer S.R., Fischer M., Baessler A., Hengstenberg C., Loewel H., Doering A., Riegger G.A., Schunkert H. No association of interleukin-6 gene polymorphism (-174G/C) with myocardial infarction or traditional cardiovascular risk factors. Int. J. Cardiol. 2004, 97:205-212.
58. Love G.D., Seeman T.E., Weinstein M., Ryff C.D. Bioindicators in the MIDUS national study: protocol, measures, sample, and comparative context. J. Aging Health 2010, 22(8):1059-1080.
59. Lust J.A., Donovan K.A., Kline M.P., Greipp P.R., Kyle R.A., Maihle N.J. Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. Cytokine 1992, 4:96-100.
60. Lutgendorf S.K., Garand L., Buckwalter K.C., Reimer T.T., Hong S.Y., Lubaroff D.M. Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. J. Gerontol. A Biol. Sci. Med. Sci. 1999, 54:M434-M439.
61. Marchio A., Tiollais P., Dejean A. Differential expression and ligand regulation of the retinoic acid receptor alpha and beta genes. EMBO J. 1989, 8:429-433.
62. Marinou I., Walters K., Winfield J., Bax D.E., Wilson A.G. A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility. Ann. Rheum. Dis. 2010, 69:1191-1194.
63. May U., Schiffelholz T., Baier P.C., Krueger J.M., Rose-John S., Scheller J. IL-6-trans-signalling increases rapid-eye-movement sleep in rats. Eur. J. Pharmacol. 2009, 613:141-145.
64. McGue M., Bouchard T.J. Adjustment of twin data for the effects of age and sex. Behav. Genet. 1984, 14:325-343.
65. Mehra R., Storfer-Isser A., Kirchner H.L., Johnson N., Jenny N., Tracy R.P., Redline S. Soluble interleukin 6 receptor: a novel marker of moderate to severe sleep-related breathing disorder. Arch. Intern. Med. 2006, 166:1725-1731.
66. Miller G. Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behav. Immun. 2003, 17:276-285.
67. Miller G.E., Stetler C.A., Carney R.M., Freedland K.E., Banks W.A. Clinical depression and inflammatory risk markers for coronary heart disease. Am. J. Cardiol. 2002, 90:1279-1283.
68. Mohamed-Ali V., Goodrick S., Bulmer K., Holly J.M., Yudkin J.S., Coppack S.W. Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am. J. Physiol. 1999, 277:E971-E975.
69. Montero-Julian F.A. The soluble IL-6 receptors: serum levels and biological function. Cell. Mol. Biol. 2001, 47:583-597.
70. Müllberg J., Schooltink H., Stoyan T., Günther M., Graeve L., Buse G., Mackiewicz A., Heinrich P.C., Rose-John S. The soluble interleukin-6 receptor is generated by shedding. Eur. J. Immunol. 1993, 23:473-480.
71. Nauck M., Winkelmann B.R., Hoffmann M.M., Böhm B.O., Wieland H., März W. The interleukin-6 G(-174)C promoter polymorphism in the LURIC cohort: no association with plasma interleukin-6, coronary artery disease, and myocardial infarction. J. Mol. Med. 2002, 80:507-513.
72. Navarro S.L., Brasky T.M., Schwarz Y., Song X., Wang C.Y., Kristal A.R., Kratz M., White E., Lampe J.W. Reliability of serum biomarkers of inflammation from repeated measures in healthy individuals. Cancer Epidemiol. Biomarkers Prev. 2012, 21:1167-1170.
73. Neale, M., Boker, S., Xie, G., Maes, H., 2003. Mx: statistical modeling. VCU Box 900126, Richmond, VA, 6th edition.
74. Nichols R.C., Bilbro J. The diagnosis of twin zygosity. Hum. Hered. 1966, 16:265-275.
75. Nikolopoulos G.K., Dimou N.L., Hamodrakas S.J., Bagos P.G. Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. J. Clin. Periodontol. 2008, 35:754-767.
76. O'Connor M.-F., Motivala S.J., Valladares E.M., Olmstead R., Irwin M.R. Sex differences in monocyte expression of IL-6: role of autonomic mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 293:R145-R151.
77. Pankow J.S., Folsom A.R., Cushman M., Borecki I.B., Hopkins P.N., Eckfeldt J.H., Tracy R.P. Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis 2001, 154:681-689.
78. Patel A., Zhu Y., Kuzhikandathil E.V., Banks W.A., Siegel A., Zalcman S.S. Soluble interleukin-6 receptor induces motor stereotypies and co-localizes with gp130 in regions linked to cortico-striato-thalamo-cortical circuits. PLoS One 2012, 7:e41623. 10.1371/journal.pone.0041623.
79. Peters M., Müller A.M., Rose-John S. Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 1998, 92:3495-3504.
80. Pini M., Rhodes D.H., Castellanos K.J., Hall A.R., Cabay R.J., Chennuri R., Grady E.F., Fantuzzi G. Role of IL-6 in the resolution of pancreatitis in obese mice. J. Leukoc. Biol. 2012, 91:957-966.
81. Posthuma D., Boomsma D.I. Mx scripts library: structural equation modeling scripts for twin and family data. Behav. Genet. 2005, 35:499-505.
82. Purcell S. Variance components models for gene-environment interaction in twin analysis. Twin Res. 2002, 5:554-571.
83. Rafiq S., Frayling T., Murray A., Hurst A. A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun. 2007, 8:552-559.
84. Reich D., Patterson N., Ramesh V., De Jager P.L., McDonald G.J., Tandon A., et al. Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels. Am. J. Hum. Genet. 2007, 80:716-726.
85. Rodríguez-Rodríguez L., Lamas J.R., Varadé J., López-Romero P., Tornero-Esteban P., Abasolo L., et al. Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity. Rheumatol. Int. 2011, 31:409-413.
86. Rooks C., Veledar E., Goldberg J., Bremner J.D., Vaccarino V. Early trauma and inflammation: role of familial factors in a study of twins. Psychosom. Med. 2012, 74:146-152.
87. Saijo Y., Kiyota N., Kawasaki Y., Miyazaki Y., Kashimura J., Fukuda M., Kishi R. Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects. Diabetes Obes. Metab. 2004, 6:249-258.
88. Saiki R., Hayashi D., Ikuo Y., Nishimura K., Ishii I., Kobayashi K., Chiba K., Toida T., Kashiwagi K., Igarashi K. Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells. J. Neurochem. 2013, 127(5):652-659.
89. Salman B.N., Vahabi S., Movaghar S.E., Mahjour F. Proliferative and inductive effects of cyclosporin a on gingival fibroblast of child and adult. Dent. Res. J. (Isfahan) 2013, 10:52-58.
90. Sas A.A., Jamshidi Y., Zheng D., Wu T., Korf J., Alizadeh B.Z., Spector T.D., Snieder H. The age-dependency of genetic and environmental influences on serum cytokine levels: a twin study. Cytokine 2012, 60:108-113.
91. Sasayama D., Hori H., Teraishi T., Hattori K., Ota M., Matsuo J., Kawamoto Y., Kinoshita Y., Amano N., Kunugi H. Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults. J. Neural Transm. 2012, 119:313-318.
92. Schöbitz B., Pezeshki G., Pohl T. Soluble interleukin-6 (IL-6) receptor arguments central effects of IL-6 in vivo. FASEB J. 1995, 6:659-664.
93. Schousboe K., Willemsen G., Kyvik K.O., Mortensen J., Boomsma D.I., Cornes B.K., Davis C.J., Fagnani C., Hjelmborg J., Kaprio J., De Lange M., Luciano M., Martin N.G., Pedersen N., Pietiläinen K.H., Rissanen A., Saarni S., Sørensen T.I.A., Van Baal G.C.M., Harris J.R. Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries. Twin Res. 2003, 6:409-421.
94. Sedgwick P. Intraclass correlation coefficient. BMJ 2013, 346:f1816.
95. Segal N., Feng R., McGuire S. Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings. Int. J. Obes. 2008, 33:37-41.
96. Semlali A., Witoled C., Alanazi M., Rouabhia M. Whole cigarette smoke increased the expression of TLRs, HBDs, and proinflammory cytokines by human gingival epithelial cells through different signaling pathways. PLoS One 2012, 7:e52614. 10.1371/journal.pone.0052614.
97. Sen A., Paine S., Chowdhury I. Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level on the acute inflammation and neovascularization stages of patients with Eales' disease. Mol. Vis. 2011, 17:2552-2563.
98. Seo H.S., Larsimont D., Ma Y., Laios I., Leclercq G. Regulation of estrogen receptor levels by ligand-induced release of compound(s) in MCF-7 cells. Mol. Cell. Endocrinol. 2000, 164:19-29.
99. Shah T., Zabaneh D., Gaunt T., Swerdlow D.I., Shah S., Talmud P.J., Day I.N., Whittaker J., Holmes M.V., Sofat R., Humphries S.E., Kivimaki M., Kumari M., Hingorani A.D., Casas J.P. Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers. Circ. Cardiovasc. Genet. 2013, 6:163-170.
100. Smith A., Zheng D., Palmen J., Pang D. Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus. Genes Immun. 2012, 13:583-586.
101. Stenberg A. Interpreting estimates of heritability - a note on the twin decomposition. Econ. Hum. Biol. 2012, 11:201-205.
102. Stephens O.W., Zhang Q., Qu P., Zhou Y., Chavan S., Tian E., Williams D.R., Epstein J., Barlogie B., Shaughnessy J.D. An intermediate-risk multiple myeloma subgroup is defined by sIL-6r: levels synergistically increase with incidence of SNP rs2228145 and 1q21 amplification. Blood 2012, 119:503-512.
103. Su S., Snieder H., Miller A., Ritchie J. Genetic and environmental influences on systemic markers of inflammation in middle-aged male twins. Atherosclerosis 2008, 200:213-220.
104. Suganami T., Ogawa Y. Adipose tissue macrophages: their role in adipose tissue remodeling. J. Leukoc. Biol. 2010, 88:33-39.
105. Tan Q., Ohm Yvik K., Kruse T.A., Christensen K. Dissecting complex phenotypes using the genomics of twins. Funct. Integr. Genomics 2010, 10:321-327.
106. Van Dongen J., Jansen R., Smit D., Hottenga J.-J., Mbarek H., Willemsen G., Kluft C., Penninx B.W.J., Ferreira M.A., Boomsma D.I., de Geus E.J.C. The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels. Behav. Genet. 2014, 44(4):368-382.
107. Van Oijen M., Arp P.P., de Jong F.J., Hofman A., Koudstaal P.J., Uitterlinden A.G., Breteler M.M.B. Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study. Neurosci. Lett. 2006, 402:113-117.
108. Vaughn C., Ochs-Balcom H., Nie J. No association between circulating levels and genetic variants of IL-6 and TNF-α and colon adenoma. Gastroenterol. Res. 2013, 6:43-48.
109. Volanakis J. Human C-reactive protein: expression, structure, and function. Mol. Immunol. 2001, 38:189-197.
110. Walston J.D., Fallin M.D., Cushman M., Lange L., Psaty B., Jenny N., Browner W., Tracy R., Durda P., Reiner A. IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study. Hum. Genet. 2007, 122:485-494.
111. Wang H., Zhang Z., Chu W., Hale T., Cooper J.J., Elbein S.C. Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity. J. Clin. Endocrinol. Metab. 2005, 90:1123-1129.
112. Weisberg S.P., Mccann D., Desai M., Rosenbaum M., Leibel R.L., Ferrante A.W. Obesity is associated with macrophage accumulation. J. Clin. Invest. 2003, 112:1796-1808.
113. Welsh P., Polisecki E., Robertson M., Jahn S., Buckley B.M., De Craen A.J.M., Ford I., Jukema J.W., Macfarlane P.W., Packard C.J., Stott D.J., Westendorp R.G.J., Shepherd J., Hingorani A.D., Smith G.D., Schaefer E., Sattar N. Unraveling the directional link between adiposity and inflammation: a bidirectional Mendelian randomization approach. J. Clin. Endocrinol. Metab. 2010, 95:93-99.
114. Wernstedt I., Eriksson A.-L., Berndtsson A., Hoffstedt J., Skrtic S., Hedner T., Hultén L.M., Wiklund O., Ohlsson C., Jansson J.-O. A common polymorphism in the interleukin-6 gene promoter is associated with overweight. Int. J. Obes. Relat. Metab. Disord. 2004, 28:1272-1279.
115. Wisse B.E. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J. Am. Soc. Nephrol. 2004, 15:2792-2800.
116. Wörns M.A., Victor A., Galle P.R., Höhler T. Genetic and environmental contributions to plasma C-reactive protein and interleukin-6 levels-a study in twins. Genes Immun. 2006, 7:600-605.
117. Yang Y., Zhang F., Skrip L., Lei H., Wang Y., Hu D., Ding R. IL-6 gene polymorphisms and CAD risk: a meta-analysis. Mol. Biol. Rep. 2012, 6:2589-2598. 10.1007/s11033-012-2345-x.
118. Zhang H.-Y., Feng L., Wu H., Xie X.-D. The association of IL-6 and IL-6R gene polymorphisms with chronic periodontitis in a Chinese population. Oral Dis. 2013, 10.1111/odi.12075.
119. Zhou X., An G., Chen J. Inhibitory effects of hydrogen sulphide on pulmonary fibrosis in smoking rats via attenuation of oxidative stress and inflammation. J. Cell Mol. Med. 2014, 1-6. 10.1111/jcmm.12254.