Interleukin-6 Receptor Gene Variations, Plasma Interleukin-6 Levels, and Type 2 Diabetes in U.S. Women
Article Figures & Tables
Figures
- FIG. 1.
Pairwise LD matrix for IL6R genes. D′ is presented above the diagonal and r2 is presented below the diagonal. (Please see http://dx.doi.org/10.2337/db07-0505 for a high-quality digital representation of this figure.)
- FIG. 2.
The geometric means of log(IL-6) (plasma IL-6, in ng/ml) by the genotypes of SNP7 (rs8192284) stratified by obese status (30 kg/m2 as a cutoff), smoking (never versus current or past smoking), alcohol consumption (0 g/day as a cutoff), and physical activity (6.0 MET h/week as a cutoff). The analyses were conducted in nondiabetic women with IL-6 measurement. Covariates, including age, BMI, smoking, alcohol consumption, physical activity, family history of diabetes, and menopausal status, were adjusted when they were not used as the strata variables. Genotypes: □, AA;□, AC; ▒, CC.
Tables
- TABLE 1
Age and age-adjusted clinical characteristics of healthy control and diabetic case subjects with IL-6 measurement (1989–1990)
Healthy control subjects Diabetic patients P n 706 642 Age (years) 56 ± 8 56 ± 8 0.90 BMI (kg/m2) 26.5 ± 6.2 30.6 ± 5.6 <0.001 Physical activity (MET h/week) 14.9 ± 17.8 12.2 ± 15.0 0.003 Alcohol consumption (g/day) 5.80 ± 9.87 2.83 ± 6.57 <0.001 Current smoker (%) 11.7 12.9 0.48 Postmenopausal status (%) 78.9 81.3 0.27 Log(IL-6) (ng/ml) 0.64 ± 0.70 0.90 ± 0.69 <0.001 Data are means ± SD or percent.
- TABLE 2
Log(IL-6) by IL6R genotypes in healthy control and diabetes case subjects
Healthy women P* FDR Diabetic women P* FDR 11 12 22 11 12 22 SNP1 246 317 114 223 299 99 0.66 ± 0.04 0.61 ± 0.04 0.68 ± 0.06 0.51 0.60 0.85 ± 0.04 0.92 ± 0.04 0.86 ± 0.07 0.34 0.45 SNP2 409 243 37 394 208 25 0.64 ± 0.03 0.62 ± 0.04 0.76 ± 0.11 0.94 0.94 0.92 ± 0.03 0.85 ± 0.05 0.99 ± 0.14 0.29 0.41 SNP3 222 357 112 215 303 110 0.61 ± 0.05 0.66 ± 0.04 0.68 ± 0.07 0.38 0.47 0.88 ± 0.04 0.91 ± 0.04 0.87 ± 0.06 0.62 0.69 SNP4 238 341 107 235 309 87 0.54 ± 0.04 0.67 ± 0.04 0.76 ± 0.07 0.005 0.02 0.81 ± 0.04 0.90 ± 0.04 1.10 ± 0.07 0.018 0.05 SNP5 215 345 114 176 325 119 0.72 ± 0.05 0.63 ± 0.04 0.50 ± 0.06 0.039 0.07 0.99 ± 0.05 0.90 ± 0.04 0.77 ± 0.06 0.035 0.07 SNP6 225 355 105 225 312 96 0.51 ± 0.05 0.68 ± 0.04 0.75 ± 0.07 0.0008 0.008 0.80 ± 0.04 0.91 ± 0.04 1.08 ± 0.07 0.01 0.03 SNP7 239 347 105 227 308 88 0.51 ± 0.04 0.69 ± 0.04 0.76 ± 0.07 0.0005 0.008 0.79 ± 0.04 0.91 ± 0.04 1.11 ± 0.07 0.004 0.02 SNP8 476 197 17 448 171 12 0.65 ± 0.03 0.64 ± 0.05 0.45 ± 0.17 0.66 0.69 0.92 ± 0.03 0.80 ± 0.05 1.19 ± 0.18 0.12 0.20 SNP9 405 253 27 362 237 32 0.69 ± 0.03 0.57 ± 0.04 0.53 ± 0.13 0.02 0.05 0.96 ± 0.03 0.82 ± 0.04 0.74 ± 0.11 0.008 0.03 SNP10 462 218 17 412 198 19 0.68 ± 0.03 0.55 ± 0.05 0.64 ± 0.17 0.026 0.06 0.92 ± 0.03 0.86 ± 0.05 0.65 ± 0.15 0.23 0.35 Data are n or means±SE. For each polymorphism, 11 represents the major allele homozygotes, 12 represents the heterozygotes, and 22 represents the minor allele homozygotes; missing genotyping is not included.
- *
* Comparisons between carriers and noncarriers; adjusted for age, BMI, alcohol consumption, smoking, physical activity, family history of diabetes, and menopausal status.
- TABLE 3
Plasma levels (log transformed) of IL-6 according to IL6R haplotypes in nondiabetic women
Haplotypes Frequency Difference in log(IL-6) (95% CI) P Global P SNP5 SNP7 SNP8 SNP9 SNP10 1 2 1 1 1 37.6 0.0 1 1 2 1 1 15.8 −0.11 (−0.23 to −0.01) 0.05 0.01 2 1 1 1 1 18.2 −0.12 (−0.22 to −0.03) 0.01 2 1 1 2 1 4.6 −0.17 (−0.38 to 0.04) 0.12 2 1 1 2 2 17.5 −0.15 (−0.27 to −0.03) 0.01 Haplotype coding: 1 represents the common allele and 2 represents the minor allele; analyses were adjusted for age and BMI.
- TABLE 4
Distribution of IL6R polymorphisms in diabetic and control subjects
SNPs Gene region Genotypes Frequency P value FDR Case subjects Control subjects SNP1 Exon 1 GG 238 (36.6) 347 (34.0) 0.43 0.84 GA 311 (47.8) 493 (48.3) AA 102 (15.6) 180 (17.7) SNP2 Intron 1 TT 414 (63.0) 625 (60.3) 0.42 0.84 TC 215 (32.7) 357 (34.4) CC 28 (4.3) 55 (5.3) SNP3 Intron 1 TT 223 (33.9) 353 (34.1) 0.59 0.84 TA 315 (47.9) 513 (49.6) AA 119 (18.1) 168 (16.3) SNP4 Intron 1 CC 241 (36.5) 372 (36.0) 0.55 0.84 CT 327 (49.5) 498 (48.2) TT 92 (14.0) 164 (15.8) SNP5 Intron 1 AA 185 (28.6) 323 (31.7) 0.34 0.84 AC 338 (52.3) 521 (51.2) CC 123 (19.1) 174 (17.1) SNP6 Intron 6 TT 231 (34.9) 354 (34.3) 0.97 0.97 TG 330 (49.8) 518 (50.2) GG 101 (15.3) 160 (15.5) SNP7 Exon 9 AA 233 (35.7) 372 (35.9) 0.96 0.97 AC 327 (50.1) 510 (49.1) CC 93 (14.2) 156 (15.0) SNP8 Intron 9 TT 471 (71.3) 715 (68.8) 0.16 0.84 TC 178 (26.9) 290 (27.9) CC 12 (1.8) 34 (3.3) SNP9 Intron 9 AA 375 (56.8) 614 (59.4) 0.58 0.84 AG 252 (38.2) 372 (36.0) GG 33 (5.0) 48 (4.6) SNP10 Exon 10 GG 426 (64.6) 696 (66.5) 0.88 0.97 (3′ untranslated region) GA 213 (32.3) 321 (30.7) AA 20 (3.1) 29 (2.8) Data are n (%), unless otherwise indicated. The missing genotyping is not counted.
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