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Arterioscler Thromb Vasc Biol 34(7): 1522-1530.

Otway, R., et al. (2007). \of atrial fibrillation?\

Qian, Y., et al. (2015). \Han population.\

Shi, Y. Y. and L. He (2005). \and genetic association at polymorphism loci.\

Takagi, T., et al. (2007). \295-300.

Tan, J. T., et al. (2009). \variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.\

Thomas, G. N., et al. (1999). \hypertension.\

Tsai, F. J., et al. (2010). \PLoS Genet 6(2): e1000847.

Ullrich, S., et al. (2005). \Unoki, H., et al. (2008). \in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.\

Xu, Y., et al. (2013). \

Yasuda, K., et al. (2008). \in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.\Nat Genet 40(9): 1092-1097.

Zeggini, E., et al. (2007). \of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.\Science 316(5829): 1336-1341.

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Han

Zhang, W., et al. (2015). \rs2237892 of KCNQ1 Is Potentially Associated with Hypertension and Macrovascular Complications in Type 2 Diabetes Mellitus in A Chinese Han Population.\Zhang, X., et al. (2012). \of single nucleotide polymorphisms in TCF2 with type 2 diabetes susceptibility in a Han Chinese population.\

Zhou, X., et al. (2016). \Diabetes Mellitus Patients.\

Table. 1 Clinical characteristics of hypertension with T2DM in subjects

Parameters

CC

Age(years) Gender(male/female)

BMI(kg/m2) SBP(mmHg) DBP(mmHg) FPG(mM) TC(mM) TG(mM) LDL-C(mM) HDL-C(mM) HbA1c

57¡À11.7 2/5 26.44¡À3.1 140.71¡À16.3 82.29¡À8.92 8.19¡À2.31 4.35¡À1.14 2.93¡À3.06 2.64¡À0.91 0.99¡À0.15 8.32¡À1.76

rs2237895

AC+AA 56¡À8.44 58/29 27.22¡À3.11 139.33¡À15.2 85.57¡À10.98 8.52¡À2.96 4.17¡À1.09 3.99¡À17.85 2.61¡À0.98 2.63¡À14.00 8.04¡À1.35

P value 0.774 0.094 0.529 0.820 0.446 0.774 0.663 0.876 0.932 0.759 0.648

CC 56.43¡À9.36 32/19 27.18¡À3.01 138.54¡À14.34 85.61¡À10.85 8.74¡À2.76 4.19¡À0.97 1.94¡À1.54 2.66¡À0.87 1.03¡À0.23 8.17¡À1.16

rs2237892

CT+TT 55.69¡À7.82 28/16 27.09¡À3.26 140.57¡À16.42 84.89¡À10.92 8.18¡À3.07 4.16¡À1.24 2.14¡À1.81 2.55¡À1.09 1.01¡À0.19 7.94¡À1.62

P value 0.452 0.466 0.785 0.123 0.722 0.710 0.102 0.359 0.226 0.719 0.236

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Table. 2 Genotype distribution and Allele frequency of rs2237895 and rs2237892 in KCNQ1 gene in T2DM complicated with HBP patients

SNPs Group Genotype distribution and frequency P value

OR (95%CI)

1.9551(0.753-5.077)

Allele frequency P value 0R (95%CI)

AA

case

rs2237895

48(0.511)

AC 39(0.415)

CC 7(0.074)

0.359

A 135(0.718)

C 53(0.282)

0.215

1.311(0.854-2.013)

control 47(0.456) 42(0.408) 14(0.136) 136(0.660) 70(0.340)

rs2237892

case

CC 56(0.549)

CT 38(0.373)

TT 8(0.078)

0.167

1.699(0.977-2.952)

C 150(0.735)

T 54(0.265)

0.098

1.43(0.956-2.185)

control 43(0.417) 50(0.485) 10(0.097) 136(0.660) 70(0.340)

Table. 3 Haplotype analysis of rs2237895 and rs2237892 in KCNQ1 associated with

hypertension with T2DM by case control comparison

Haplotype homozygous wild type heterozygous wild type Sum up

homozygous+heterozygous

Wild type

105(0.558) 83 (0.441)

67 (0.325) 139(0.674)

Case 26(0.277) 15(0.159) 53(0.564) 15(0.159)

control 12(0.117) 48(0.680) 43(0.417) 48(0.466)

P value 6¡Á10-6

4¡Á10-5

1.6¡Á10-6

2.62 (1.742-3.954)

OR 6.93 (2.828-16.997)

3.94 (1.948-7.988)

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Table. 4 Association between genotypes of rs2237895, rs2237892 and clinician parameters

rs2237895

rs 2237892

rs2237895

rs 2237892

Parameters

P value

P value

Parameters

P value

P value

AC+AA CC

CC CT+TT AC+AA CC CC CT+TT Gender

Age (years)

Male 15 2 11 6 ¨R60 15 2 11 6 Female

16 2

1.00 10 8

0.302

< 60 13 3

0.656

8 8

0.211

BMI(kg/m2)

BMI(kg/m2)

¨R25 18 2 12 8 ¨R25 15 4 11 8 < 25 6 2 0.555 6 2 0.669 < 25 3 1 1.00 3 1 1.00 SBP (mmHg)

SBP (mmHg)

¨R140 14 2 10 6 ¨R140 11 4 11 4 < 140 15 2 1.00 10 7 0.420 < 140 14 1 0.330 7 8 0.264 DBP (mmHg) DBP (mmHg)

¨R 90 5 0 3 2 ¨R 90 5 2 6 1 < 90 24 4 1.00 17 11 1.00 < 90 20 3 0.565 12 11 0.193 FPG (mM)

FPG (mM)

¨R 7.0 19 3 12 10 ¨R 7.0 16 4 12 8 < 7.0 10 1 1.00 8 3 0.456 < 7.0 9 1 0.640 6 4 1.00 TC (mM)

TC (mM)

¨R 5.72 0 2 3 1 ¨R 5.72 2 2 2 2 < 5.72 29 2 0.010 19 14 0.633 < 5.72 23 3 0.119 10 16 1.00 TG (mM)

TG (mM) ¨R 1.7. 8 3 8 3 ¨R 1.7. 9 2 7 4 < 1.7 21 1 0.097 12 10 0.456 < 1.7 16 3 1.00 0 8 0.03 LDL-C (mM)

LDL-C (mM)

¨R 3.3 5 2 5 2 ¨R 3.3 7 2 5 4 < 3.3 24 2 0.190 15 11 0.431 < 3.3 18 3 0.622 13 8 1.00 HDL-C(mM)

HDL-C(mM)

¨R1.0/1.3 7 0 5 2 ¨R1.3 3 0 2 1 < 1.0/1.3 21 4 1.00 15 10 0.683 < 1.3 21 5 1.00 16 10 0.684 HbA1c (%)

HbA1c (%)

¨R6.5 22 2 14 10 ¨R6.5 21 4 16 9 < 6.5

0 1

0.068

1 0

1.00

< 6.5

0 0

1.00

0 0

1.00

a. Association of genotypes with parameters in over 60 group

b. Association of genotypes with parameters in female group

14

rs2237895

rs 2237892

Parameters

Pvalue

P value

AC+AA CC CC CT+TT Age (years)

¨R60 16 2 10 8 < 60 35 0

0.119

18 17

0.393

BMI(kg/m2)

¨R25 37 1 20 18 < 25 11 1 0.426 8 4 0.512 SBP (mmHg)

¨R140 28 0 11 17 < 140 23 2 0.336 17 8 0.021 DBP (mmHg)

¨R 90 23 0 11 12 < 90 28 2 0.623 17 13 0.269 FPG (mM)

¨R 7.0 36 1 20 17 < 7.0 15 1 0.517 8 8 0.397 TC (mM)

¨R 5.72 5 0 2 3 < 5.72 46 2 0.417 26 22 0.658 TG (mM) ¨R 1.7. 19 2 12 9 < 1.7 31 0 0.295 15 16 0.276 LDL-C (mM)

¨R 3.3 12 0 7 5 < 3.3 39 2 1.00 21 20 0.242 HDL-C(mM)

¨R1.0 20 0 10 10 < 1.0 31 2 1.00 15 18 0.379 HbA1c (%)

¨R6.5 36 1 11 7 < 6.5

6 1

0.296

1 3

0.127

c. Association of genotypes with parameters in male group

Han

Figure. 1 Genotyping results for rs2237892 and rs2237895 in KCNQ1 gene

a. Genotyping result for rs2237892

CC

TT CT

b. Genotyping result for rs2237895

AC

700 bp

AA

CC

400 bp

200 bp

15

ѧÉúͶ³öÂÛÎÄSCI - ͼÎÄ

HanArteriosclerThrombVascBiol34(7):1522-1530.Otway,R.,etal.(2007).\ofatrialfibrillation?\Qian,Y.,etal.(2015).\Hanpopulation.\Shi,Y.Y.andL.He(20
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