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Aims: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM).SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis.A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047.Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.Methods: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM).SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis.A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047.Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.Results: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM).SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis.A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047.Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.Conclusions: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM).SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis.A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047.Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk. [ABSTRACT FROM AUTHOR]