#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the , , , and Loci


Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.


Vyšlo v časopise: Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the , , , and Loci. PLoS Genet 7(4): e32767. doi:10.1371/journal.pgen.1001374
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001374

Souhrn

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.


Zdroje

1. van de StolpeA

van der SaagPT

1996 Intercellular adhesion molecule-1. J Mol Med 74 13 33

2. RidkerPM

HennekensCH

Roitman-JohnsonB

StampferMJ

AllenJ

1998 Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 351 88 92

3. PradhanAD

RifaiN

RidkerPM

2002 Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation 106 820 825

4. SongY

MansonJE

TinkerL

RifaiN

CookNR

2007 Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes 56 1898 1904

5. PareG

ChasmanDI

KelloggM

ZeeRY

RifaiN

2008 Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. PLoS Genet 4 e1000118

6. BarbalicM

DupuisJ

DehghanA

BisJC

HoogeveenRC

2010 Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Hum Mol Genet 19 1863 1872

7. QiL

CornelisMC

KraftP

JensenM

van DamRM

2010 Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes. Hum Mol Genet 19 1856 1862

8. BielinskiSJ

PankowJS

FosterCL

MillerMB

HopkinsPN

2007 Circulating soluble ICAM-1 levels shows linkage to ICAM gene cluster region on chromosome 19: The NHLBI Family Heart Study follow-up examination. Atherosclerosis

9. KentJWJr

MahaneyMC

ComuzzieAG

GoringHH

AlmasyL

2007 Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans. Atherosclerosis 195 367 373

10. PonthieuxA

LambertD

HerbethB

DroeschS

PfisterM

2003 Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort. Eur J Hum Genet 11 679 686

11. PuthothuB

KruegerM

BernhardtM

HeinzmannA

2006 ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels. Genes Immun 7 322 326

12. PurcellS

DalyMJ

ShamPC

2007 WHAP: haplotype-based association analysis. Bioinformatics 23 255 256

13. PurcellS

NealeB

Todd-BrownK

ThomasL

FerreiraMA

2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575

14. PsatyBM

O'DonnellCJ

GudnasonV

LunettaKL

FolsomAR

2009 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ Cardiovasc Genet 2 73 80

15. JohanssonLE

LindbladU

LarssonCA

RastamL

RidderstraleM

2008 Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. Eur J Endocrinol 159 577 583

16. PareG

CookNR

RidkerPM

ChasmanDI

2010 On the use of variance per genotype as a tool to identify quantitative trait interaction effects: a report from the Women's Genome Health Study. PLoS Genet 6 e1000981

17. ThorgeirssonTE

GudbjartssonDF

SurakkaI

VinkJM

AminN

2010 Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42 448 453

18. Tobacco and Genetics Consortium 2010 Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 42 441 447

19. LiuJZ

TozziF

WaterworthDM

PillaiSG

MugliaP

2010 Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 42 436 440

20. XuZ

TaylorJA

2009 SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37 W600 605

21. CollinsT

ReadMA

NeishAS

WhitleyMZ

ThanosD

1995 Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J 9 899 909

22. LedeburHC

ParksTP

1995 Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-kappa B site and p65 homodimers. J Biol Chem 270 933 943

23. RomeoS

KozlitinaJ

XingC

PertsemlidisA

CoxD

2008 Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40 1461 1465

24. YuanX

WaterworthD

PerryJR

LimN

SongK

2008 Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet 83 520 528

25. KantartzisK

PeterA

MachicaoF

MachannJ

WagnerS

2009 Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58 2616 2623

26. VelazquezL

ChengAM

FlemingHE

FurlongerC

VeselyS

2002 Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice. J Exp Med 195 1599 1611

27. Newton-ChehC

JohnsonT

GatevaV

TobinMD

BochudM

2009 Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet

28. LevyD

EhretGB

RiceK

VerwoertGC

LaunerLJ

2009 Genome-wide association study of blood pressure and hypertension. Nat Genet

29. GudbjartssonDF

BjornsdottirUS

HalapiE

HelgadottirA

SulemP

2009 Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 41 342 347

30. HuntKA

ZhernakovaA

TurnerG

HeapGA

FrankeL

2008 Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 40 395 402

31. ToddJA

WalkerNM

CooperJD

SmythDJ

DownesK

2007 Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39 857 864

32. TalmudPJ

DrenosF

ShahS

ShahT

PalmenJ

2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Am J Hum Genet 85 628 642

33. SoranzoN

SpectorTD

ManginoM

KuhnelB

RendonA

2009 A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41 1182 1190

34. GaneshSK

ZakaiNA

van RooijFJ

SoranzoN

SmithAV

2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet 41 1191 1198

35. RidkerPM

ChasmanDI

ZeeRY

ParkerA

RoseL

2008 Rationale, Design, and Methodology of the Women's Genome Health Study: A Genome-Wide Association Study of More Than 25 000 Initially Healthy American Women. Clin Chem 54 249 255

36. RegisterTC

BurdonKP

LenchikL

BowdenDW

HawkinsGA

2004 Variability of serum soluble intercellular adhesion molecule-1 measurements attributable to a common polymorphism. Clin Chem 50 2185 2187

37. EschenO

ChristensenJH

DethlefsenC

SchmidtEB

2008 Cellular Adhesion Molecules in Healthy Subjects: Short Term Variations and Relations to Flow Mediated Dilation. Biomark Insights 3 57 62

38. WiggintonJE

CutlerDJ

AbecasisGR

2005 A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 76 887 893

39. PriceAL

PattersonNJ

PlengeRM

WeinblattME

ShadickNA

2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909

40. FrazerKA

BallingerDG

CoxDR

HindsDA

StuveLL

2007 A second generation human haplotype map of over 3.1 million SNPs. Nature 449 851 861

41. Pe'erI

YelenskyR

AltshulerD

DalyMJ

2008 Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32 381 385

42. PurcellSM

WrayNR

StoneJL

VisscherPM

O'DonovanMC

2009 Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460 748 752

43. McVeanGA

MyersSR

HuntS

DeloukasP

BentleyDR

2004 The fine-scale structure of recombination rate variation in the human genome. Science 304 581 584

44. WincklerW

MyersSR

RichterDJ

OnofrioRC

McDonaldGJ

2005 Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308 107 111

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2011 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#