title: CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression in monocytes.
abstract: Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in immune responses. In the current study, we investigated the association of two CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to pneumonia-induced sepsis and examined the effects of these two polymorphisms on gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed that frequencies of the rs1129055GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI], 0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the other polymorphism, rs17281995G/C, revealed significantly increased numbers in pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20, p=0.025). Further analyses about CD86 gene expression revealed that both messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes from controls carrying rs17281995GC genotype than those carrying wild-type rs17281995GG genotype (p=0.022 and p=0013). These results suggest that polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia-induced sepsis, in which rs17281995G/C may increase the risk of the disease by interfering gene expression of CD86 in monocytes.
authors.affiliation: Department of Internal Medicine, Emergency Center, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.
authors.forename: Haihan
authors.initials: H
authors.lastname: Song
authors.forename: Lunxian
authors.initials: L
authors.lastname: Tang
authors.forename: Mingzheng
authors.initials: M
authors.lastname: Xu
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Li
authors.forename: Shumin
authors.initials: S
authors.lastname: Xu
authors.forename: Guanggang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Bao
authors.forename: Bingke
authors.initials: B
authors.lastname: Sun
authors.forename: Tingting
authors.initials: T
authors.lastname: Cheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Bai
mesh_terms: D051940:B7-2 Antigen / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011014:Pneumonia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen