PMID- 28472164 OWN - NLM STAT- MEDLINE DCOM- 20170915 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 5 DP - 2017 TI - Association study of MCP-1 promoter polymorphisms with the susceptibility and progression of sepsis. PG - e0176781 LID - 10.1371/journal.pone.0176781 [doi] LID - e0176781 AB - Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin-1 beta (IL-1beta) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-alpha (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications. FAU - He, Junbing AU - He J AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Chen, Yuhua AU - Chen Y AD - The Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong, China. FAU - Lin, Yao AU - Lin Y AD - The Department of Stomatology, Jieyang Affiliated Hospital, SunYat-sen University, Jieyang, Guangdong, China. FAU - Zhang, Wenying AU - Zhang W AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Cai, Yujie AU - Cai Y AD - Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Chen, Feng AU - Chen F AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Liao, Qinghui AU - Liao Q AD - The Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong, China. FAU - Yin, Zihan AU - Yin Z AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Wang, Yan AU - Wang Y AD - Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Tao, Shoubao AU - Tao S AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Lin, Xiaoli AU - Lin X AD - The Department of Stomatology, Jieyang Affiliated Hospital, SunYat-sen University, Jieyang, Guangdong, China. FAU - Huang, Pengru AU - Huang P AD - Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Cui, Lili AU - Cui L AD - Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Shao, Yiming AU - Shao Y AUID- ORCID: 0000-0003-1769-6502 AD - The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. LA - eng PT - Journal Article DEP - 20170504 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Chemokine CCL2) SB - IM MH - Aged MH - Chemokine CCL2/*genetics MH - Disease Progression MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - *Promoter Regions, Genetic MH - Sepsis/*genetics PMC - PMC5417587 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/05/05 06:00 MHDA- 2017/09/16 06:00 PMCR- 2017/05/04 CRDT- 2017/05/05 06:00 PHST- 2017/02/08 00:00 [received] PHST- 2017/04/17 00:00 [accepted] PHST- 2017/05/05 06:00 [entrez] PHST- 2017/05/05 06:00 [pubmed] PHST- 2017/09/16 06:00 [medline] PHST- 2017/05/04 00:00 [pmc-release] AID - PONE-D-17-01353 [pii] AID - 10.1371/journal.pone.0176781 [doi] PST - epublish SO - PLoS One. 2017 May 4;12(5):e0176781. doi: 10.1371/journal.pone.0176781. eCollection 2017.