Introduction 2000 2003 1997 2000 2006 2006 2007 2007 2007 2007 2007 2007 FTO 2007 2007 2007 2007 2007 2007 2007 2008 2008 2008 2008 2007 2008 FTO FTO 2 2 FTO Materials and methods Study subjects 2 2 2 2 1 2 Table 1 Clinical characterization of obese and control subjects Obese Control P Gender (M/F) 419/508 658/842 Age (year) 49.1 ± 14.2 48.2 ± 16.5 0.049 2 34.50 ± 5.39 21.65 ± 2.08 <0.000001 Glucose (mg/dl) 129.2 ± 49.6 97.7 ± 23.9 <0.000001 HbA1c (%) 6.5 ± 1.8 5.1 ± 0.6 <0.000001 Total cholesterol (mg/dl) 209.9 ± 37.9 201.2 ± 36.4 <0.000001 Triglycerides (mg/dl) 153.2 ± 99.5 104.0 ± 73.2 <0.000001 High-density lipoprotein cholesterol (mg/dl) 53.1 ± 18.9 65.1 ± 15.7 <0.000001 Systolic blood pressure (mmHg) 136.4 ± 18.1 123.4 ± 17.8 <0.000001 Diastolic blood pressure (mmHg) 83.8 ± 12.0 76.0 ± 11.1 <0.000001 P U DNA preparation and SNP genotyping FTO 2001 2002 2007 Statistical analysis 2 2007 2 P P 2 1998 2005 U Results Case-control association studies FTO FTO 2 2 P P P a ar ar 2 a r r a 2002 r 1 P 2007 2007 2007 D' r 2  1 P P P 2 FTO Fig. 1 P FTO P P D' upper gray bar Table 2 FTO dbSNP ID Allele Genotype Additive mode Recessive mode Dominant mode Case Control 1/2 11 12 22 Sum 11 12 22 Sum OR (95% CI) χ2 P χ2 P OR (95% CI) χ2 P OR (95% CI) rs9937053 A/G 59 360 494 913 63 414 773 1250 1.31 (1.13–1.51) 12.3 0.00047 2.0 0.16 1.30 (0.90–1.88) 13.0 0.00031 1.37 (1.16–1.63) rs9939973 A/G 61 367 496 924 75 504 941 1520 1.32 (1.15–1.51) 15.7 a 3.0 0.081 1.36 (0.96–1.93) 16.1 a 1.40 (1.19–1.66) rs9940128 A/G 60 366 498 924 75 500 941 1516 1.31 (1.15–1.50) 15.2 a 2.6 0.11 1.33 (0.94–1.89) 15.9 a 1.40 (1.19–1.65) rs1421085 C/T 49 338 537 924 57 443 1019 1519 1.38 (1.20–1.59) 19.6 a 3.3 0.068 1.44 (0.97–2.12) 20.0 a 1.47 (1.24–1.74) rs1558902 A/T 48 341 536 925 52 449 1021 1522 1.41 (1.22 -1.62) 21.2 a 4.6 0.032 1.55 (1.04–2.31) 20.8 a 1.48 (1.25–1.75) rs1121980 A/G 61 367 499 927 73 504 947 1524 1.33 (1.16–1.52) 16.5 a 3.6 0.059 1.40 (0.99–1.99) 16.5 a 1.41 (1.19–1.66) rs7193144 C/T 49 339 532 920 55 447 1014 1516 1.39 (1.21–1.61) 20.4 a 4.0 0.044 1.49 (1.01–2.22) 20.3 a 1.47 (1.24–1.74) rs8043757 T/A 48 319 541 908 54 436 1027 1517 1.36 (1.18–1.57) 17.4 a 4.2 0.040 1.51 (1.02–2.25) 16.4 a 1.42 (1.20–1.69) rs8050136 A/C 51 336 538 925 56 450 1018 1524 1.38 (1.20–1.59) 19.4 a 4.7 0.031 1.53 (1.04–2.26) 18.5 a 1.45 (1.22–1.71) rs3751812 T/G 51 340 534 925 55 458 1013 1526 1.38 (1.20–1.59) 19.6 a 5.1 0.024 1.56 (1.06–2.31) 18.5 a 1.45 (1.22–1.71) rs9923233 C/G 51 335 533 919 55 449 1010 1514 1.38 (1.20–1.60) 19.8 a 5.0 0.025 1.56 (1.06–2.30) 18.7 a 1.45 (1.23–1.72) rs9926289 A/G 50 323 531 904 56 425 993 1474 1.37 (1.19 -1.58) 18.7 a 3.9 0.047 1.48 (1.00–2.19) 18.1 a 1.45 (1.22–1.72) rs9939609 A/T 51 334 534 919 56 443 1005 1504 1.38 (1.20–1.59) 19.5 a 4.5 0.034 1.52 (1.03–2.24) 18.7 a 1.45 (1.23–1.72) rs7185735 G/A 51 340 536 927 55 455 1014 1524 1.38 (1.20–1.59) 19.9 a 5.0 0.025 1.55 (1.05–2.30) 18.8 a 1.45 (1.23–1.72) rs9931494 G/C 64 363 494 921 71 504 942 1517 1.35 (1.18–1.55) 18.4 a 5.6 0.018 1.52 (1.07–2.15) 16.9 a 1.42 (1.20–1.67) rs17817964 T/C 62 361 500 923 68 524 930 1522 1.30 (1.14–1.49) 13.5 0.00022 5.8 0.016 1.54 (1.08–2.19) 11.4 0.00075 1.33 (1.13–1.57) rs9930506 G/A 67 365 488 920 82 521 913 1516 1.28 (1.12–1.46) 12.8 0.00038 3.5 0.061 1.37 (0.98–1.92) 12.1 0.00051 1.34 (1.14–1.58) rs9932754 C/T 66 368 491 925 78 525 919 1522 1.29 (1.13–1.48) 13.6 0.00023 4.2 0.040 1.42 (1.01–2.00) 12.6 0.00040 1.35 (1.14–1.59) rs9922619 T/G 66 368 489 923 78 529 919 1526 1.29 (1.13–1.48) 13.5 0.00024 4.3 0.038 1.43 (1.02–2.01) 12.3 0.00044 1.34 (1.14–1.58) rs7204609 C/T 134 418 373 925 273 717 529 1519 0.83 (0.73–0.93) 9.68 0.0022 5.0 0.025 0.77 (0.62–0.97) 7.5 0.0063 0.79 (0.67–0.94) rs12149832 A/G 53 349 525 927 62 480 982 1524 1.33 (1.15–1.53) 15.2 a 3.5 0.061 1.43 (0.98–2.08) 14.8 a 1.39 (1.17–1.64) The odds ratio (OR) for each SNP was adjusted simultaneously for age and gender using additive model CI χ 2 a P P Analysis of various quantitative phenotypes with rs1558902 3 Table 3 Comparison of various quantitative phenotypes among different genotypes at single nucleotide polymorphism (SNP) rs1558902 in obese and control subjects Obese Control n n n n n n Age (year) 49.8 ± 15.3 49.6 ± 14.3 48.8 ± 14.1 46.9 ± 15.4 46.9 ± 16.7 48.8 ± 16.5 P 0.64 0.098 2 35.16 ± 5.70 34.61 ± 5.43 34.39 ± 5.33 21.94 ± 2.23 21.62 ± 2.10 21.65 ± 2.06 P 0.58 0.56 Glucose (mg/dl) 142.8 ± 54.8 125.4 ± 43.2 130.8 ± 53.3 101.7 ± 44.1 96.3 ± 18.1 98.2 ± 24.7 P 0.054 0.34 HbA1c (%) 6.9 ± 2.1 6.4 ± 1.7 6.5 ± 1.8 5.1 ± 1.2 5.0 ± 0.5 5.1 ± 0.7 P 0.19 0.15 Total cholesterol (mg/dl) 215.1 ± 46.7 211.3 ± 38.8 208.6 ± 36.6 195.6 ± 38.8 201.4 ± 37.8 201.4 ± 35.6 P 0.37 0.53 Triglycerides (mg/dl) 171.7 ± 119.5 151.3 ± 102.1 153.2 ± 96.0 111.7 ± 70.6 102.0 ± 71.4 104.4 ± 74.2 P 0.42 0.63 HDL cholesterol (mg/dl) 53.2 ± 13.8 54.8 ± 24.0 52.0 ± 15.4 62.1 ± 14.2 65.1 ± 15.9 65.3 ± 15.6 P 0.14 0.53 SBP (mmHg) 134.2 ± 20.4 137.0 ± 17.8 136.2 ± 18.2 122.7 ± 17.3 123.2 ± 18.8 123.5 ± 17.5 P 0.61 0.91 DBP (mmHg) 80.3 ± 11.7 84.1 ± 12.0 83.9 ± 12.0 75.5 ± 11.1 75.2 ± 11.7 76.3 ± 10.9 P 0.14 0.22 P HDL SBP DBP 4 Table 4 Association of body mass index (BMI) with rs1558902 genotypes in the Japanese general population AA AT TT P a 2 n 23.17 ± 3.20 (59) 22.79 ± 3.26 (482) 22.57 ± 3.11 (1063) 0.041 a Discussion FTO 2007 2007 2007 FTO 2007 2007 2007 2007 2008 2008 2008 2007 2008 2008 2007 2008 FTO FTO P 2 2002 2 1998 FTO FTO FTO FTO 2007 2007 FTO 2007 2007 SCG3 2007 MTMR9 2007 2000 2006 FTO Electronic supplementary material Below is the link to the electronic supplementary material. Summary of the association of SNPs between cases and controls (DOC 315 kb)