Studies On The Relationship Between Single Nucleotide Polymorphisms And Susceptibility To Coronary Heart Disease In Chinese Population

Background and Objectivecoronary heart disease (CHD) is one of the most frequently occurringcardiovascular diseases in the world, and has always been an emphasis of medicalresearch in our country. For the latent CHD, lack of clinical sympotoms, neithersimply nor non-invasively laboratory evaluations are available. While the acutecoronary syndrome, with an acute onset, rapid progression and high mortality,severely threatens the public. Early detection and resection for CHD by screening ofhigh-risk population are therefore very important to decrease the mortality andincrease the survival rate.Traditionally epidemiological studies show that hypertension, diabetes mellitus,hyperlipidemia, cigarette smoking, and obesity are major risk factors. On the otherhand, genetic factors are believed to play a key role in CHD susceptibility.Single nucleotide polymorphism (SNP) is one of the most common types ofDNA sequence variations, taking the form of substitutions at a single base pair. Inaddition to being responsible for phenotypic variation, this minor variation amongindividuals can also promote susceptibility to disease. When a large number ofdisease carrying patients and unrelated groups of individuals are analyzed for allelicassociations, a particular allele may occur more frequently in patients than the normalcontrol. To clarify the etiological effect of four SNPs on CHD, including GCLCC-129T,GCLM C-588T,GCLM C-23T and OLR1 3'UTR C188T, a sample size ofover 200 cases-controls pairs is included in this study.Materials and methods245 cases of CHD and 242 controls were recruited from March 2004 toSeptember 2005 from the Tongji Hospital, Shanghai, China. The genotypes of GCLCC-129T,GCLM C-23T,GCLM C-588T and OLR1 3'UTR C188T were determinedby a PCR based RFLP method.Odds radios (ORs) for CHD and 95％confidence intervals (CIs) fromunconditional logistic regression models were used to evaluate relative risks. In the multivariate analyses, potential risk factors were included in the logistic regressionmodels as covariates. A P value of＜0.05 was considered significant. All aboveanalyses were performed using SPSS 10.0 software (SPSS, Chicago, IL).Hardy-Weinberg equilibrium tests, allelotype-specific ORs and Armitage's trend testswere performed using website-based software at http://ihg.gsf.de/ihg/snps.html.Results1. The T allele of GCLC C-129T was significantly associated with the presenceof CHD and had a 1.38-fold increased risk of CHD (95％CI 1.25-4.54, P=0.007)compared to the C allele. Compared to C/C homozygote, T-allele carriers had a1.28-fold significantly increased risk (95％CI=1.16-4.49, P=0.017) of CHD. Thisepidemiological study suggests that T/T homozygote of GCLC C-129T is potentiallyone of the genetic risk factors for CHD in Chinese population.2. The T allele of GCLM C-588T/G-23T was significantly associated with thepresence of CHD and had a 0.41-fold decreased risk of CHD (95％CI 0.40～0.88, P=0.009) compared to the C allele. Compared to -588CC/-23GG homozygote,-588CT/-23GT heterozygote had a 0.33-fold decreased risk (95％CI=0.45～1.01, P=0.056), whereas -588TT/-23TT homozygote had a 0.80-fold significantly decreasedrisk (95％CI=0.06～0.61, P=0.005) of CHD. This large epidemiological studysuggests that -588TT/-23TT homozygote of GCLM C-588T/G-23T is potentially oneof the risk genetic protective factorss for CHD in Chinese population.3. There was no significant difference among genotypes of OLR1 3'UTRC188T for the risks for CHD in this study.Conclusions1. Carriers of GCLC -129T allele have a significantly increased risk for CHD.The findings suggests that GCLC C-129T is one of the genetic risk factors for CHD.2. The T allele of GCLM C-588T/G-23T was associated with the decreased riskof CHD and -588TT/-23TT homozygote is potentially one of the risk geneticprotective factorss for CHD in Chinese populationa.3. All SNPs in this study occurs at a minimal allele frequency of＞1％inChinese population. OLR1 3'UTR C188T may be, at least in this population,unrelated with CHD risks. In summary, our data provide the first molecular epidemiological evidence thatGCLC C-129T,GCLM G-588T,GCLM C-23T are genetic factors for CHD amongthe Chinese population. This finding may prove helpful in identifying susceptibleindividuals, ultimately facilitating effective intervention.