Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene single nucleotide polymorphisms and its interaction with T2DM on pulmonary tuberculosis in Chinese Uygur population
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Xian-Hua Wang1, Ai-Guo Ma1, Xiu-Xia Han1, Lei Chen1, Hui Liang1, Aishan-Litifu2, Abudumijit-Ablez2 and Feng Xue3
1The School of Public Health, Medical College of Qingdao University, Qingdao, P.R China
2Department of Respiratory Medicine, Xinjiang Uygur Autonomous Region Chest Hospital, The Xinjiang Uygur Autonomous Region, Urumqi, P.R China
3Tuberculosis Department of The Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, The Xinjiang Uygur Autonomous Region, Urumqi, P. R China
Xiu-Xia Han, email: [email protected]
Keywords: pulmonary tuberculosis, PTPN22, single nucleotide polymorphisms, interaction, T2DM
Received: March 13, 2017 Accepted: April 23, 2017 Published: July 15, 2017
Aims: To 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.
Methods: A 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.
Results: Logistic 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.
Conclusions: We 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.
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