A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with acute coronary syndrome.
OBJECTIVE
Evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). We hypothesized that the -1C/T polymorphism of the CD40 gene would be associated with ACS and influence the CD40 expression.


METHODS
The genotype distribution and allele frequency of CD40-1C/T polymorphism in 248 ACS patients and 206 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Monocytes from 90 healthy volunteers were incubated with IFN-gamma. CD40 expression was detected by flow cytometry.


RESULTS
Patients with ACS showed a significant increase of CD40 expression compared with controls (P<0.001). The frequency of the CC genotype in the ACS group was significantly higher than that of the controls (P<0.001). Frequency of the C allele was higher among ACS patients compared with controls (P<0.001). Case control association analysis of the CD40 -1C/T SNP showed an association between the C allele and ACS (OR=1.991, 95%CI: 1.526 approximately 2.596, P<0.001). -1C/C carriers presented significantly higher CD40 expression levels than -1C/T and -1T/T subjects, both in ACS group and controls (P<0.001). When stimulated by IFN-gamma, CD40 expression levels on monocytes in individuals with CC, CT and TT genotypes were increased by 9.16, 3.83 and 1.53 fold, respectively, compared with the levels absent with IFN-gamma.


CONCLUSIONS
These results suggest that the -1C allele of the CD40 (-1C/T) gene polymorphism is a genetic factor that may determine an individual's susceptibility by ACS in Chinese. The CD40 -1C/T polymorphism is a novel regulator of CD40 expression.
Tian
Caixia
C
Department of Clinical Laboratory Science, Renmin Hospital, Yunyang Medical College, Shiyan, Hubei, PR China.
Qin
Weichao
W
Li
Lian
L
Zheng
Weidong
W
Qiu
Fangcheng
F
D054058:Acute Coronary Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D003327:Coronary Disease / Q000150:complications; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D019013:CD40 Antigens; D007371:Interferon-gamma