Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene single nucleotide polymorphisms and its interaction with T2DM on pulmonary tuberculosis in Chinese Uygur population.

Xian-Hua Wang,Xiu-Xia Han,Hui Liang,Feng Xue,Ai-Guo Ma,Aishan-Litifu Aishan-Litifu,Lei Chen,Abudumijit-Ablez Abudumijit-Ablez

doi:10.18632/oncotarget.19274

Abstract

AimsTo investigate the association of several single nucleotide polymorphisms (SNPs) within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene and additional gene- gene and gene- type 2 diabetes mellitus (T2DM) interaction with pulmonary tuberculosis (PTB) risk in Chinese Uygur population.MethodsA total of 722 participants (186 males, 536 females) were selected, including 360 PTB patients and 362 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and T2DM. Logistic regression was performed to investigate association between 3 SNPs within PTPN22 gene, additional gene- gene and gene- T2DM interaction on PTB risk.ResultsLogistic regression analysis showed that PTB risk was significantly lower in carriers with rs2476601- CT genotype than those with CC genotype (CT versus CC), adjusted OR (95%CI) =0.42 (0.17-0.83), and higher in carriers with the rs33996649- GA genotype than those with GG genotype (GA versus GG), adjusted OR (95%CI) = 5.66 (2.24-9.47). We found a significant two-locus model (p=0.0010) involving rs33996649 and T2DM. Overall, the cross-validation consistency of this two- locus model was 10/ 10, and the testing accuracy was 60.11%. We also conducted stratified analysis for rs33996649 and T2DM using logistic regression. We found that T2DM patients with rs33996649 - GA genotype have the highest PTB risk, compared to non- T2DM patients with rs33996649- GG genotype, OR (95%CI) = 4.52 (2.71 -6.43), after covariates adjustment.ConclusionsWe found that the T allele of rs2476601 and the A allele of rs33996649within PTPN22 gene, interaction between rs2476601 and T2DM were all associated with increased PTB risk.

Highlights

Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases worldwide [1]
We found that the T allele of rs2476601 and the A allele of rs33996649within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene, interaction between rs2476601 and type 2 diabetes mellitus (T2DM) were all associated with increased PTB risk
Logistic regression analysis showed that PTB risk was significantly lower in carriers with rs2476601CT genotype than those with CC genotype (CT versus CC), adjusted OR (95%CI) =0.42 (0.17-0.83), and higher in carriers with the rs33996649- GA genotype than those with GG genotype (GA versus GG), adjusted OR (95%CI) = 5.66 (2.24-9.47)

Summary

Introduction

Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases worldwide [1]. The prevalence rate of PTB was significant different among several ethnic minorities [5], the differences in susceptibility to TB may be related to a genetic predisposition. Several studies have reported PTB related genetic factors previously [6,7,8]. Protein tyrosine phosphatases were involved in maintaining the T cells in the resting stage and are responsible for bringing back the activated T cells to the resting phenotype in the absence and presence of antigen, respectively [9, 10]. Several studies have reported a significant association between single nucleotide polymorphisms (SNPs) and susceptibility to several autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus (SLE) [12,13,14]

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