Influences of the common FTO rs9939609 variant on inflammatory markers throughout a broad range of body mass index.
BACKGROUND
A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men.


RESULTS
In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m(2), all of whom were above the 99(th) percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively.


CONCLUSIONS
No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.
Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark. ez@ipm.regionh.dk
Esther
E
Zimmermann
Kristin
K
Skogstrand
David M
DM
Hougaard
Arne
A
Astrup
Torben
T
Hansen
Oluf
O
Pedersen
Thorkild I A
TI
Sørensen
Tine
T
Jess
D054392:Adipokines / Q000097:blood; D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis*; D003718:Denmark; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
D054392:Adipokines; D005819:Genetic Markers; D011506:Proteins; D002097:C-Reactive Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
Trends Genet. 2010 Jun;26(6):266-74
20381893
Dis Markers. 2009;26(5-6):247-63
19773614
Science. 2007 May 11;316(5826):889-94
17434869
Diabet Med. 2005 Sep;22(9):1199-205
16108849
J Chronic Dis. 1977 Jun;30(6):359-67
874040
Hum Biol. 1981 Sep;53(3):403-10
7309025
Lancet. 2010 Jan 9;375(9709):132-40
20031199
Nat Genet. 2007 Jun;39(6):724-6
17496892
Obesity (Silver Spring). 2009 Feb;17(2):330-4
18948966
PLoS One. 2008 Aug 13;3(8):e2958
18698412
Gastroenterology. 2007 May;132(6):2087-102
17498505
Nature. 2006 Dec 14;444(7121):875-80
17167476
Circulation. 2003 Jan 28;107(3):499-511
12551878
Obes Facts. 2008;1(3):138-45
20054173
Adv Med Sci. 2009;54(2):150-7
19875356
Obes Rev. 2007 May;8(3):187-9
17444960
Clin Chem. 2005 Oct;51(10):1854-66
16081507
Epidemiol Rev. 2007;29:98-114
17494057
Diabetes. 2008 Nov;57(11):3145-51
18647953
PLoS One. 2009;4(2):e4428
19214238
Circ Cardiovasc Genet. 2009 Jun;2(3):255-9
20031593
J Immunol Methods. 2008 Jul 20;336(1):78-84
18495149
Scand J Soc Med Suppl. 1989;41:1-160
2711133
J Chronic Dis. 1977 Jun;30(6):351-8
874039