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已发表论文
对 DPP4 相关变异的整合遗传分析揭示了 2 型糖尿病及心血管代谢共病的风险模式
Authors Wu S, Zuo C, Bai C, Chen Q, Qiao Y , Zhou N, Xiao Q
Received 11 November 2025
Accepted for publication 18 December 2025
Published 1 January 2026 Volume 2025:18 Pages 4843—4858
DOI https://doi.org/10.2147/DMSO.S577700
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Rebecca Baqiyyah Conway
Shuangxin Wu,1,2,* Chao Zuo,3,4,* Chuan Bai,2 Qi Chen,1 Yongchao Qiao,3 Nan Zhou,4 Qiang Xiao5
1Medical Research Center, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, People’s Republic of China; 2Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 4Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China; 5Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiang Xiao, Email xiaoq58@mail.sysu.edu.cn Nan Zhou, Email zhoun55@mail.sysu.edu.cn
Background: Hypertension (HTN) and dyslipidemia (DYS) frequently complicate type 2 diabetes mellitus (T2DM), increasing cardiovascular risk. Genetic variation within the DPP4–ABCC8–INSR–IGF1 axis may underlie this clustering.
Methods: A total of 444 T2DM patients were stratified into T2DM (n = 256), T2DM with HTN (T2MH, n = 134), and T2DM with HTN and DYS (T2MH-DYS, n = 54). Six single nucleotide polymorphisms (SNPs) were genotyped, and associations were assessed by logistic regression and haplotype analysis with Bonferroni correction.
Results: Clinical profiling showed higher C-reactive protein (CRP) and adrenocorticotropic hormone (ACTH) in T2MH and more severe metabolic derangements in T2MH-DYS. DPP4 rs3788979 was strongly linked to hypertension: CT (adjusted OR = 0.370, P = 0.001) and CC (adjusted OR = 0.424, P = 0.001) were protective versus TT, while in the T2MH vs T2MH-DYS comparison, the same CT and CC genotypes conferred increased dyslipidemia risk (adjusted OR = 5.418, P = 0.001; OR = 5.620, P = 0.002). In the comparison between T2DM and T2MH-DYS, the same genotypes also increase the susceptibility risk. IGF1 rs972936 TC genotype also reduced T2MH risk (adjusted OR = 0.460, P = 0.006). Haplotype analysis identified GAATGT as protective against hypertension (OR = 0.312, P = 0.0014) and GACCGT as a risk haplotype for dyslipidemia (OR = 4.113, P = 0.0021); both remained significant after Bonferroni correction.
Conclusion: Variants within the DPP4 axis influence susceptibility to HTN and DYS in T2DM, with GAATGT and GACCGT emerging as robust haplotype markers. Notably, the risk conferred by DPP4 rs3788979 genotypes was modulated by lipid status: CT/CC were protective against hypertension alone but became risk factors when dyslipidemia co-occurred.
Keywords: DPP4 axis, polymorphism, haplotype, type 2 diabetes, hypertension, dyslipidemia
1Medical Research Center, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, People’s Republic of China; 2Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 4Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China; 5Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiang Xiao, Email xiaoq58@mail.sysu.edu.cn Nan Zhou, Email zhoun55@mail.sysu.edu.cn
Background: Hypertension (HTN) and dyslipidemia (DYS) frequently complicate type 2 diabetes mellitus (T2DM), increasing cardiovascular risk. Genetic variation within the DPP4–ABCC8–INSR–IGF1 axis may underlie this clustering.
Methods: A total of 444 T2DM patients were stratified into T2DM (n = 256), T2DM with HTN (T2MH, n = 134), and T2DM with HTN and DYS (T2MH-DYS, n = 54). Six single nucleotide polymorphisms (SNPs) were genotyped, and associations were assessed by logistic regression and haplotype analysis with Bonferroni correction.
Results: Clinical profiling showed higher C-reactive protein (CRP) and adrenocorticotropic hormone (ACTH) in T2MH and more severe metabolic derangements in T2MH-DYS. DPP4 rs3788979 was strongly linked to hypertension: CT (adjusted OR = 0.370, P = 0.001) and CC (adjusted OR = 0.424, P = 0.001) were protective versus TT, while in the T2MH vs T2MH-DYS comparison, the same CT and CC genotypes conferred increased dyslipidemia risk (adjusted OR = 5.418, P = 0.001; OR = 5.620, P = 0.002). In the comparison between T2DM and T2MH-DYS, the same genotypes also increase the susceptibility risk. IGF1 rs972936 TC genotype also reduced T2MH risk (adjusted OR = 0.460, P = 0.006). Haplotype analysis identified GAATGT as protective against hypertension (OR = 0.312, P = 0.0014) and GACCGT as a risk haplotype for dyslipidemia (OR = 4.113, P = 0.0021); both remained significant after Bonferroni correction.
Conclusion: Variants within the DPP4 axis influence susceptibility to HTN and DYS in T2DM, with GAATGT and GACCGT emerging as robust haplotype markers. Notably, the risk conferred by DPP4 rs3788979 genotypes was modulated by lipid status: CT/CC were protective against hypertension alone but became risk factors when dyslipidemia co-occurred.
Keywords: DPP4 axis, polymorphism, haplotype, type 2 diabetes, hypertension, dyslipidemia