Variations in Adiponectin Receptor Genes and Susceptibility to Type 2 Diabetes in Women
A Tagging–Single Nucleotide Polymorphism Haplotype Analysis
Article Figures & Tables
Figures
- FIG. 1.
Pairwise LD matrix for ADIPOR1 (A) and ADIPOR2 (B) genes. D′ is presented above the diagonal, and r2 is presented below the diagonal.
- FIG. 2.
Haplotype cladogram for the ADIPOR1 gene. Gray circles represent the inferred haplotypes with their frequencies, which are proportional to the size (diameter) of the circles. P1–P6 represent the polymorphic changes (in the order of rs2232853, rs10494839, rs12733285, rs1342387, rs1139646, and rs10920531) separating one haplotype from the other.
- FIG. 3.
Sliding window analyses of the associations between ADIPOR2 haplotypes (possessing two to six SNPs) and the risk of type 2 diabetes. −log10 P values of global tests for the haplotype windows are presented as solid diamonds. The haplotype windows for a given number of SNPs (two to six) were generated by grouping the corresponding number of SNPs in the order of the position of polymorphisms and moving one SNP each time from 5′ to 3′ end.
Tables
- TABLE 1
Polymorphisms in ADIPOR1 and ADIPOR2 genes
Polymorphisms Allele Position Location MAF ADIPOR1 rs2232853 G>A −11760 5′ promoter 0.28 rs10494839 T>C −1896 Intron 1 0.28 rs12733285 C>T −1742 Intron 1 0.31 rs1342387 C>T 5843 Intron 4 0.46 rs1139646* C>G 10225 Exon 8–3′ UTR 0.32 rs10920531 C>A 11363 3′ UTR 0.37 ADIPOR2 rs11061925 C>T −60276 Intron 1 0.29 rs7132033 G>C −57414 Intron 1 0.27 rs7975600 T>A −48258 Intron 1 0.13 rs11061937 T>C −46897 Intron 1 0.30 rs12826079 C>T −36954 Intron 1 0.07 rs11061946 G>A −34983 Intron 1 0.07 rs10773983 C>T −32264 Intron 1 0.32 rs11612383 C>T −32155 Intron 1 0.32 rs1058322 C>T −26531 Intron 1 0.31 rs12230440 T>G −6557 Intron 1 0.15 rs929434 G>A −1421 Intron 1 0.30 rs11061971 A>T 218 Intron 2 0.44 rs11061973 G>A 2426 Intron 2 0.14 rs2108642 C>A 3289 Intron 2 0.46 rs7316374 G>A 7621 Intron 2 0.14 rs1044471 C>T 33446 3′ UTR 0.48 -
Alleles are presented as common allele>minor allele. Location of polymorphism is relative to the translation start point.
- *
* rs1139646 is also known as rs7539542.
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- TABLE 2
Genotype distributions of polymorphism in ADIPOR1 and ADIPOR2 genes in diabetic case and control subjects
Polymorphisms Case (%)/control (%) by genotype Odds ratio (95% CI) Homozygote, major Heterozygote Homozygote, minor Crude Adjusted* ADIPOR1 rs2232853 341 (49.1)/565 (51.4) 297 (42.7)/440 (40.0) 57 (8.2)/94 (8.6) 1.10 (0.91–1.33) 1.16 (0.94–1.43) rs10494839 340 (48.7)/557 (51.1) 296 (42.4)/438 (40.2) 62 (8.9)/95 (8.7) 1.11 (0.91–1.34) 1.17 (0.95–1.44) rs12733285 344 (49.4)/511 (47.1) 293 (42.0)/485 (44.7) 60 (8.6)/88 (8.2) 0.91 (0.75–1.10) 0.87 (0.70–1.07) rs1342387 210 (30.4)/297 (27.8) 347 (50.4)/558 (52.3) 132 (19.2)/212 (19.9) 0.88 (0.71–1.09) 0.77 (0.61–0.98) rs1139646 290 (43.2)/513 (48.7) 306 (45.5)/433 (41.1) 76 (11.3)/108 (10.2) 1.26 (1.03–1.53) 1.36 (1.10–1.70) rs10920531 266 (37.9)/464 (42.6) 329 (46.9)/470 (43.1) 107 (15.2)/156 (14.3) 1.21 (1.00–1.47) 1.33 (1.08–1.65) ADIPOR2 rs11061925 336 (48.4)/552 (50.7) 301 (43.3)/429 (39.4) 58 (8.3)/108 (9.9) 1.10 (0.90–1.32) 1.22 (0.99–1.51) rs7132033 363 (51.5)/587 (53.2) 292 (41.4)/419 (37.9) 50 (7.1)/98 (8.9) 1.07 (0.88–1.29) 1.18 (0.96–1.46) rs7975600 521 (75.7)/814 (75.7) 156 (22.7)/236 (22.0) 11 (1.6)/25 (2.3) 1.00 (0.80–1.25) 1.02 (0.80–1.31) rs11061937 334 (48.0)/518 (48.1) 296 (42.5)/444 (41.3) 66 (9.5)/114 (10.6) 1.01 (0.83–1.22) 1.12 (0.90–1.38) rs12826079 617 (87.6)/959 (86.7) 85 (12.1)/143 (12.9) 2 (0.3)/4 (0.4) 0.92 (0.69–1.22) 1.01 (0.74–1.38) rs11061946 594 (84.4)/941 (85.0) 104 (14.8)/160 (14.5) 6 (0.8)/6 (0.5) 1.05 (0.81–1.36) 1.08 (0.81–1.44) rs10773983 306 (44.5)/492 (45.5) 317 (46.1)/464 (42.9) 65 (9.4)/125 (11.6) 1.04 (0.86–1.26) 1.05 (0.85–1.30) rs11612383 335 (47.6)/496 (45.9) 297 (42.2)/475 (44.0) 72 (10.2)/109 (10) 0.93 (0.77–1.13) 0.98 (0.80–1.21) rs1058322 323 (46.6)/514 (48.0) 300 (43.3)/448 (41.8) 70 (10.1)/109 (10.2) 1.06 (0.87–1.28) 1.12 (0.91–1.38) rs12230440 476 (70.7)/745 (70.8) 184 (27.4)/288 (27.4) 13 (1.9)/19 (1.8) 1.00 (0.81–1.24) 1.10 (0.87–1.39) rs929434 321 (47.2)/496 (47.6) 295 (43.3)/435 (41.8) 65 (9.5)/110 (10.6) 1.02 (0.84–1.24) 1.13 (0.91–1.40) rs11061971 216 (31.4)/335 (31.2) 337 (49.0)/510 (47.6) 135 (19.6)/227 (21.2) 0.99 (0.80–1.22) 1.09 (0.86–1.37) rs11061973 501 (72.7)/783 (72.1) 173 (25.1)/284 (26.1) 15 (2.2)/19 (1.8) 0.97 (0.78–1.20) 1.02 (0.80–1.28) rs2108642 195 (28.1)/313 (28.8) 343 (49.4)/516 (47.4) 156 (22.5)/259 (23.8) 1.03 (0.84–1.28) 1.16 (0.92–1.46) rs7316374 542 (76.6)/818 (74.1) 156 (22.0)/267 (24.2) 10 (1.4)/19 (1.7) 0.88 (0.70–1.09) 0.89 (0.70–1.13) rs1044471 185 (27.3)/319 (29.6) 329 (48.4)/514 (47.8) 165 (24.3)/243 (22.6) 1.12 (0.91–1.39) 1.11 (0.87–1.40) -
rs1139646 is also known as rs7539542.
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* Adjusted for age, BMI, alcohol consumption, smoking, physical activity, family history of diabetes, and menopausal status—under dominant inheritance mode.
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- TABLE 3
Distributions of haplotypes* inferred from ADIPOR1 polymorphisms in diabetic case and control subjects
rs2232853 rs10494839 rs12733285 rs1342387 rs1139646 rs10920531 Frequency OR (95% CI)† P Cases Controls 1 1 0 0 0 0 0.255 0.243 1.0 — 0 0 1 1 0 0 0.188 0.208 0.76 (0.61–0.96) 0.02 0 0 0 0 1 1 0.206 0.189 1.00 (0.80–1.23) 0.94 0 0 0 1 0 0 0.113 0.120 0.85 (0.66–1.10) 0.22 0 0 1 1 1 1 0.080 0.063 1.28 (0.93–1.75) 0.13 Haplotypes <5% 0.157 0.176 0.78 (0.61–0.98) 0.03 -
Global test: −2log-likehood = 15.1 on 5 df, P = 0.0098.
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* 0 codes the common allele, and 1 codes the minor allele.
- †
† Adjusted for age, BMI, alcohol consumption, smoking, physical activity, and menopausal status.
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