1.68 85.98 52.1 17.8 8.2 21.9 t-value p-value two.272 2.01 six.04 26.42 35.37 0.02 0.03 0.07 0 0 H p – value adjusted for age. ��p-value adjusted for age and pack years. FEV1/FEV6. Pack years were calculated by multiplying the amount of bidis smoked per day with number of years of smoking, and then dividing the item by 24 . doi:10.1371/journal.pone.0089957.t001 0.011 respectively) and with FEV1/FVC under recessive model. The G Hesperidin manufacturer allele of GSTP1 showed significant damaging association with FEV1 below additive and recessive models and with FEV1/FVC beneath recessive model. The association of rs1695 below recessive model with FEV1 remained important even just after correction for various testing. The G allele of MMP12 showed significant positive association with FEV1 below dominant model and with FEV1/FVC beneath additive and dominant models. Two SNPs in IREB2 showed marginal constructive association with only FEV1 under recessive model. The T allele 17493865 of TGF-b showed association with FEV1/FVC under dominant model. Three SNPs in SERPINE2, showed considerable positive association with both the phenotypes beneath recessive model. The p values remained significant after correction for many testing only for FEV1. Making use of a SC1 web sliding window method we generated haplotypes of two, three and four SNPs and analyzed their association with COPD, FEV1 and FEV1/FVC. The haplotypes showing nominal substantial association are presented in table S3. Haplotypes carrying the G allele of rs2276109 had a substantial protective impact against developing COPD. Haplotypes of MMP12 carrying the A allele of both rs652438 and rs2276109 conferred considerable danger of building the disease. The IREB2 haplotypes containing the important alleles of rs2568494, rs2656069, rs10851906, rs965604 and minor alleles of rs1964678 and rs12593229 showed substantial negative association with each COPD and lung function Model# A, R A, R D R R R R R Model# R R A, D R R R GENE FAM13A GSTP1 MMP12 SERPINE2 SERPINE2 SERPINE2 IREB2 IREB2 TGF b SNP ID rs7671167 rs1695 rs2276109 rs729631 rs975278 rs7583463 rs2568494 rs10851906 rs1800469 Allele T G G G A A A G T b- FEV1 23.913, 26.773 23.425, 213.25 6.557 210.89 210.89 29.523 9.445 six.524 P1 0.013, 0.011 0.043, 0.001 0.050 0.002 0.002 0.002 0.052 0.052 P-FDR 0.302, 0.087 0.694, 0.026 0.943 0.026 0.026 0.026 0.275 0.275 b-FEV1/FVC 24.436 27.184 six.024, 7.095 27.195 27.195 26.655 P2 0.036 0.023 0.015, 0.007 0.011 0.011 0.007 P-FDR 0.290 0.220 0.371, 0.359 0.133 0.133 0.133 3.857 0.028 D 0.4467 P1: p-value for FEV1 adjusted for age and pack years. P2: p-value for FEV1/FVC adjusted for age and pack years. P-FDR: p-value corrected for a number of hypothesis testing by BenjaminiHochberg False Discovery Price method. # A: Additive, R: Recessive, D: Dominant. doi:10.1371/journal.pone.0089957.t002 three COPD in South Indian Male Smokers parameters. The SERPINE2 haplotypes containing main alleles of rs729631, rs975278, rs7583463 and minor allele of rs16865421 had a significantly higher frequency in controls and were positively associated with lung 26001275 function. The two SNP haplotype of GSTP1 containing the minor allele G of rs1695 was negatively connected with FEV1. This effect appeared to become profound when in combination using the threat haplotype AA of MMP12. Nonetheless, G allele of rs1695 didn’t appear to become enough enough to generate the detrimental effect when in combination together with the protective haplotype AG of MMP12. The 2, 3 and four SNP haplotypes constructed out of SNPs from the genes studied.1.68 85.98 52.1 17.8 eight.2 21.9 t-value p-value two.272 2.01 six.04 26.42 35.37 0.02 0.03 0.07 0 0 H p – value adjusted for age. ��p-value adjusted for age and pack years. FEV1/FEV6. Pack years have been calculated by multiplying the amount of bidis smoked every day with number of years of smoking, then dividing the product by 24 . doi:ten.1371/journal.pone.0089957.t001 0.011 respectively) and with FEV1/FVC under recessive model. The G allele of GSTP1 showed substantial negative association with FEV1 below additive and recessive models and with FEV1/FVC beneath recessive model. The association of rs1695 under recessive model with FEV1 remained significant even following correction for several testing. The G allele of MMP12 showed important constructive association with FEV1 below dominant model and with FEV1/FVC below additive and dominant models. Two SNPs in IREB2 showed marginal positive association with only FEV1 under recessive model. The T allele 17493865 of TGF-b showed association with FEV1/FVC below dominant model. 3 SNPs in SERPINE2, showed substantial positive association with each the phenotypes beneath recessive model. The p values remained important after correction for many testing only for FEV1. Applying a sliding window approach we generated haplotypes of 2, three and four SNPs and analyzed their association with COPD, FEV1 and FEV1/FVC. The haplotypes showing nominal important association are presented in table S3. Haplotypes carrying the G allele of rs2276109 had a significant protective impact against creating COPD. Haplotypes of MMP12 carrying the A allele of each rs652438 and rs2276109 conferred substantial danger of developing the illness. The IREB2 haplotypes containing the significant alleles of rs2568494, rs2656069, rs10851906, rs965604 and minor alleles of rs1964678 and rs12593229 showed significant adverse association with both COPD and lung function Model# A, R A, R D R R R R R Model# R R A, D R R R GENE FAM13A GSTP1 MMP12 SERPINE2 SERPINE2 SERPINE2 IREB2 IREB2 TGF b SNP ID rs7671167 rs1695 rs2276109 rs729631 rs975278 rs7583463 rs2568494 rs10851906 rs1800469 Allele T G G G A A A G T b- FEV1 23.913, 26.773 23.425, 213.25 6.557 210.89 210.89 29.523 9.445 6.524 P1 0.013, 0.011 0.043, 0.001 0.050 0.002 0.002 0.002 0.052 0.052 P-FDR 0.302, 0.087 0.694, 0.026 0.943 0.026 0.026 0.026 0.275 0.275 b-FEV1/FVC 24.436 27.184 6.024, 7.095 27.195 27.195 26.655 P2 0.036 0.023 0.015, 0.007 0.011 0.011 0.007 P-FDR 0.290 0.220 0.371, 0.359 0.133 0.133 0.133 three.857 0.028 D 0.4467 P1: p-value for FEV1 adjusted for age and pack years. P2: p-value for FEV1/FVC adjusted for age and pack years. P-FDR: p-value corrected for many hypothesis testing by BenjaminiHochberg False Discovery Rate approach. # A: Additive, R: Recessive, D: Dominant. doi:ten.1371/journal.pone.0089957.t002 3 COPD in South Indian Male Smokers parameters. The SERPINE2 haplotypes containing key alleles of rs729631, rs975278, rs7583463 and minor allele of rs16865421 had a considerably higher frequency in controls and were positively related with lung 26001275 function. The two SNP haplotype of GSTP1 containing the minor allele G of rs1695 was negatively associated with FEV1. This effect appeared to become profound when in combination with the danger haplotype AA of MMP12. Nevertheless, G allele of rs1695 didn’t appear to become enough enough to produce the detrimental impact when in mixture together with the protective haplotype AG of MMP12. The 2, three and 4 SNP haplotypes constructed out of SNPs with the genes studied.
