CTLA‐4 gene polymorphism and its association with Graves’ disease in the Lebanese population

Graves’ disease is an organ‐specific autoimmune disease that has a female predominance. It is probably the result of a complex interaction of genetic and environmental factors. This disease is characterized by immune system activation, evidenced by elevated serum thyroid‐specific autoantibodies and lymphocytic infiltration of the target organ (the thyroid gland), associated with raised levels of circulating activated T lymphocytes. Several reports have demonstrated genetic linkage and association between the genetic markers of the CTLA‐4 gene on chromosome 2q33 and Graves’ disease. In order to confirm this association in the Lebanese population, a bi‐allelic A/G polymorphism at position 49 of CTLA‐4 exon 1 was studied in 34 patients with Graves’ disease, and in 38 healthy individuals, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. The results showed a significant increase in allele and genotype frequencies in patients with Graves’ disease compared to controls. This suggests that the CTLA‐4 gene might play a role in the development of Graves’ disease in the Lebanese population.     

CTLA‐4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus erythematosus patients

Cytotoxic T lymphocyte‐associated antigen‐4 is a cell‐surface molecule providing a negative signal for T cell activation. CTLA‐4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA‐4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA‐4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27–5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99–3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non‐AA (39.2 ± 11.5 vs. 31.6 ± 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA‐4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA‐4 +49.     

CTLA-4 +49A/G polymorphism is associated with Behçet's disease in a Tunisian population

The involvement of excessive T-helper cell functions in the pathogenesis of Behçet's disease (BD) has been reported. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays a role in T-cell downregulation. In this report, we investigated the possible association between BD patients and the CTLA-4 +49A/G polymorphism in Tunisian population. A total of 135 Tunisian BD patients and 151 healthy blood donors from the same geographic area were genotyped by polymerase chain reaction for the CTLA-4 +49 A/G polymorphism. A highly significant difference between Tunisian BD patients and healthy controls was found regarding the distribution of CTLA-4 +49 A allele [ P  < 10⁻⁷; χ² = 75.63; odds ratio (OR) = 4.63; 95% confidence interval (CI) = 3.20–6.72] and genotype frequencies ( P  < 10⁻⁷; χ² = 71.02). Furthermore, in the BD group, the A allele was predominant in males (76.3%) when compared with females (62%), ( P  = 0.014; χ² = 5.97; OR = 1.99; 95% CI = 1.10–3.59). No relationship was found between the studied genotype and clinical manifestations. Our results show a gene dose effect of the A allele on the BD. The A allele exerts a stronger effect on disease susceptibility in males compared with females.     

The association of CTLA‐4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population

Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA‐4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA‐4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case–control design. Two single nucleotide polymorphisms (SNPs) in the CTLA‐4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA‐4+49A/G located in exon 1 of the CTLA‐4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17–3.73) using allele‐based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02–8.58). No correlations of at‐risk genotype (G/G) of CTLA‐4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA‐4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.     

The association between matrix metalloproteinase-7 genetic variant and bladder cancer risk in a Chinese Han population

Clinical and Experimental Medicine - The circulating matrix metalloproteinase-7 (MMP-7) levels are associated with the risk of bladder cancer (BC). MMP-7 gene -181A/G polymorphism may influence the...     

Association of TIM4 promoter polymorphism −1419G>A with childhood asthma in a Chinese Han population

TIM4, which is expressed on dendritic cells and macrophages, plays an important role in the proliferation of T helper type 2 (Th2) cells. Asthma, as a complex genetic disease, is thought to arise from the development of a Th2-lymphocyte-predominant immune response. To evaluate the effects of the promoter polymorphisms (-1419G>A and -1609G>A) in TIM4 on asthma susceptibility, case-control and family-based association studies were conducted by polymerase chain reaction and restriction fragment length polymorphism. Our results showed that TIM4 -1419G>A polymorphism was associated with asthma susceptibility in our study population (χ²= 9.88, P < 0.001, OR = 1.91, 95% CI 1.37–2.64). The -1419A/A and -1419A/G genotypes were observed more common in asthmatic group (6.3%, 41.8%) than in control group (1.7%, 29.3%). No significant difference was found in genotype and allele frequencies of TIM4 -1619G>A polymorphism between asthmatic and control groups. No association between the two SNPs and total serum IgE levels, lung function was observed. In conclusion, the present findings suggest that TIM4 -1419G>A polymorphism might be the genetic factor for the risk of childhood asthma in Chinese Han population.     

No association between thrombospondin-4 A387P polymorphism and acute coronary syndrome in Chinese Han population

Objective: The thrombospondin-4 (TSP-4) gene G29926C (A387P) polymorphism was recently reported to be associated with an increased risk of MI (myocardial infarction) in American population. However, several subsequent studies produced controversial findings. The aim of this study was to explore the possible association between TSP-4 A387P polymorphism and ACS (acute coronary syndrome) in Chinese Han population. Methods :A case-control study including 412 patients with ACS and 337 controls free from CAD (coronary artery disease) was conducted. TSP-4 A387P polymorphism was determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism) analysis. Results:Slightly decreased frequency of GC genotype was observed in patients with ACS, compared with controls (5.3% vs. 7.1%), but the difference did not reach statistical significance (P = 0.31 ). Similarly, the prevalence of C allele was 2.7% and 3.6% for ACS and control groups, respectively (P = 0.32). None of homozygote was detected for C allele. Further analyses in subjects subgrouped according to sex and age also showed no association of TSP-4 A387P polymorphism with ACS. Furthermore, after adjustment for conventional risk factors by multiple logistic regression analysis, the carrier prevalence of C allele did not differ significantly between ACS and control groups (OR = 0.85; 95% CI:0.45-1.59; P = 0.60). Conclusion:The present study suggested that the TSP-4 A387P variant showed a low prevalence compared with western populations and failed to associate with an altered risk of ACS in Chinese Han population. The findings further supplement experimental data for TSP-4 gene study of coronary disease.     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

The association of TAP polymorphisms with non-small-cell lung cancer in the Han Chinese population

The host immune system plays a crucial role in multiple types of cancer, including non-small-cell lung cancer (NSCLC). Transporter associated with antigen processing (TAP) protein heterodimer complexes might promote intracellular antigen peptide binding with class I major histocompatibility complex (MHC-I) molecules, and in recent years, TAP1 and TAP2 have been reported to be associated with multiple cancer risks. In the current study, we investigated the association of single-nucleotide polymorphisms (SNPs) in TAP1 and TAP2 with NSCLC in a Han Chinese population. Six and seven TAP1 and TAP2 SNPs, respectively, were genotyped and analysed in healthy controls and NSCLC patients. Based on our data, none of the six SNPs in TAP1 is associated with NSCLC risk (P > 0.0038). However, rs2228396 alleles in TAP2 were significantly different between NSCLC patients and healthy controls, and the A allele might be associated with an increased risk of this cancer (P = 0.001, OR = 1.65, 95%CI: 1.23 ∼ 2.21). Moreover, the genotype frequencies of rs2228396 were significantly different between patients and healthy controls (P = 7 × 10⁻⁴). Additionally, TAP2 rs241441 alleles exhibited a trend of difference between NSCLC patients and healthy controls, with the C allele possibly being associated with increased risk of NSCLC (P = 0.013; OR = 1.30, 95%CI: 1.06 ∼ 1.60). Moreover, the genotypes of rs241441 in TAP2 showed a significant difference between NSCLC patients and healthy controls (P = 1 × 10⁻⁴). In haplotype analysis, the TAP2 SNP haplotype (CAC, TAP2*0102) was significantly associated with increased NSCLC risk in the Han Chinese population (P = 0.003; OR = 1.57, 95%CI: 1.17 ∼ 2.10). Our results indicate that TAP2 SNPs (rs2228396 and rs241441) have a potential role in NSCLC pathogenesis.     

The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population

Growing evidence suggests that the Thr241Met (T241M) polymorphism in the homologous recombination repair gene XRCC3 may alter DNA repair capacity and subsequent susceptibility to carcinogens. In a few studies of colorectal cancer (CRC), however, the results have been discrepant. A population-based nested case-control study including 140 cases and 280 cancer-free controls was conducted to evaluate the effect of XRCC3 polymorphism, environmental exposure, and family history (FH) on the risk of CRC. The variant allele frequency was low among the ethnic Han Chinese, but we observed a significant difference between cases (6.07%) and controls (2.32%). The analytic results of the unconditional logistic regression model adjusted by age, sex, alcohol intake, cigarette smoking, and FH of cancer in first-degree relatives showed a significantly increased risk of CRC (adjusted odds ratio [OR] = 3.13, 95% confidence interval [CI]: 1.41-6.95, P = 0.005) as the T/M and M/M genotypes compared with the T/T genotype, which changed weakly in consideration of the subsite (adjusted OR = 4.80, 95%CI: 1.77-12.98, P = 0.002 in colon cancer, adjusted OR = 2.41, 95%CI: 0.93-6.25, P = 0.071 in rectal cancer, respectively). Combined with environmental factors such as alcohol intake and cigarette smoking, no significant interaction could be found. However, the results revealed a significant association between FH of cancer in first-degree relatives and the risk of CRC (adjusted OR = 2.24, 95%CI: 1.18-4.25, P = 0.014). These results also suggest that XRCC3 T241M polymorphism and FH of cancer may be risk factors for CRC, and the XRCC3 241Met allele may be an effective biomarker for genetic susceptibility to CRC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.     

The association of SERPINE2 gene with COPD in a Chinese Han population

Purpose

Polymorphisms of several candidate genes have been studied and associated with the development of chronic obstructive pulmonary disease (COPD). One such candidate is the SERPINE2 (Serpin peptidase inhibitor, clade E member 2) gene.

Materials and Methods

To assess whether the SERPINE2 gene is associated with COPD in a Chinese Han population. Samples were collected from a Chinese Han population and analyzed for the association of single nucleotide polymor phisms (SNPs) or haplotypes of SERPINE2 gene with COPD in a case-control study. Three SNPs including rs840088 G/A in intron 1, rs1438831 A/G in 5'' upstream sequence and rs3795879 G/A in intron 3 were detected using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism technique in 409 COPD subjects and 411 controls. Genotyping of the SREPINE2 polymorphisms at positions rs840088, rs1438831and rs3795879 was performed.

Results

We found that none of the rs840088G/A, rs1438831G/A and rs3795879 G/A polymorphisms were associated with the disease. The p-values were 0.630, 0.208 and 0.398 respectively.

Conclusion

Our data suggested that there was no significant association between SERPINE2 polymorphism and COPD susceptibility in the Chinese Han population.     

HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion

Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal-fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal-maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA.     

Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population

Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator, and accumulating data have provided evidence for that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). In this study, we performed a case-control study to demonstrate whether the risk for the development of onset of sporadic PD might be influenced by VDR gene polymorphisms in a Chinese cohort. Two hundred and sixty PD patients and 282 matched-healthy controls were genotyped for two representative single nucleotide polymorphisms (SNPs) in VDR gene (FokI C/T and BsmI G/A) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis in. Results from our study revealed that FokI C allele carriers were likely to associate with an increased risk of PD (P = 0.004) as well as early-onset PD (EOPD) (P = 0.010). Moreover, the frequency of FokI C allele was significantly increased in PD group and late-onset PD (LOPD) group relative to the control groups respectively (P = 0.023 and P = 0.033, respectively). For BsmI polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls, as well as gender- and age-related differences between PD patients and the controls subgroup. This study demonstrated a possible association between the VDR FokI T/C polymorphism and PD, indicating that VDR polymorphisms may well change genetic susceptibility to sporadic PD in a Han Chinese population.     

Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population

Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5 mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.     

Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention‐deficit hyperactivity disorder in Chinese Han population

Previous studies have suggested that the serotonergic (5‐HT) system might be involved in the development of Attention‐deficit hyperactivity disorder (ADHD). ADHD is frequently characterized by aggressive and impulsive behavior, a major symptom associated with reduction in serotonergic function. The tryptophan hydroxylase (TPH) gene is a reasonable candidate for ADHD because it encodes the rate‐limiting enzyme in the process of 5‐HT biosynthesis. In this study, we examined the relationship between the A218C polymorphism in TPH gene and ADHD. Sixty‐nine ADHD patients and their biological parents were investigated. The A218C polymorphism in intron 7 of TPH gene was detected by PCR‐RFLP method. No allele or genotype concerned with this A218C polymorphism was found to be associated with ADHD when analyzed with the haplotype relative risk method. Therefore, our data indicate that the TPH gene A218C polymorphism may not be a susceptibility factor of ADHD in the Chinese Han population. © 2001 Wiley‐Liss, Inc.     

Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case–control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism ‘TC’ genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35–.63), p < .001]. GC cases with dominant genetic model ‘TC + CC’ had a 47% reduced risk of GC [OR, 95%CI: .53 (.40–.71), p < .001]. Subgroup analyses revealed that the rs733618 ‘TC + CC’ genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31–.58), p < .001], those aged ≤60 years old [OR, 95%CI: .27 (.18–.42), p < .001], non-drinkers [OR, 95%CI: .21 (.13–.33), p < .001], non-smokers [OR, 95%CI: .38 (.25–.57), p < .001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10–.26), p < .001]. Further multivariated analyses indicated that individuals with the ‘TC + CC’ rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29–.83), p = .032] and had no H. pylori infection [OR, 95%CI: .35 (.28–.76), p = .018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with ‘TC’ and ‘TC + CC’ genotypes (all p < .05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.     

Association of CD28 gene polymorphism with cervical cancer risk in a Chinese population

Human papilloma virus plays a causal role in cervical carcinogenesis. However, only a small portion of infected individuals develop cervical cancer. Host genetic factors may confer susceptibility to this disease. CD28 participates in the maintenance of immune homeostasis as an important positive co‐stimulatory molecule. Allelic variation of immuno‐modulatory genes may be associated with alteration in immune function. This study investigated the associations between CD28 IVS3 +17T>C polymorphism and risk of cervical cancer in the Chinese population. Genotypes of CD28 polymorphism were detected in 619 cases with primary cervical cancer and in 985 normal controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. A higher frequency of CD28 +17TC heterozygote was determined in patients in comparison with controls (19.4% versus 12.5%). Subjects carrying at least one CD28 IVS3 +17 C allele (TC or CC genotype) had increased risk of cervical cancer (OR = 1.66, 95% CI = 1.27–2.17). This study suggests that the CD28 IVS3 +17T>C polymorphism might be genetic susceptibility factor for cervical cancer in Chinese population.     

Genetic association study between α 1‐antichymotrypsin polymorphism and Alzheimer disease in Chinese Han population

We investigated a common signal peptide polymorphism in the α 1‐antichymotrypsin (ACT) gene in 125 sporadic Alzheimer disease (AD) patients and 141 healthy control subjects in Chinese Han population. We found no significant difference in the distribution of ACT polymorphism between AD cases and controls, and failed to detect any effects of ACT genotypes associated with AD. Thus, our data do not support the involvement of ACT polymorphism in the risk of AD in Chinese Han population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:133–135, 2000. © 2000 Wiley‐Liss, Inc.     

MLH1基因415G/C多态与结肠癌遗传易感性的关联研究

目的 探讨MLH1基因415G/C多态与我国汉族人群结肠癌发生的关系.方法 收集97例散发结肠癌患者,138名正常对照,以及5个结肠癌家系的6例结肠癌患者,19名直系亲属.采用聚合酶链反应-限制性片段长度多态性分析法检测外周血MLH1基因415位点多态性.采用逆转录-聚合酶链反应检测各基因型结肠癌患者正常结肠黏膜的MLH1 mRNA表达.结果 散发结肠癌患者MLH1基因415位点CC基因型频率明显高于正常对照(P=0.035,OR=5.29,95%CI:1.07～26.04).结肠癌家系中患者和直系亲属的C等位基因的频率明显高于散发患者和正常对照(P=0.003和P=0.006).各基因型结肠癌患者正常结肠黏膜的MLH1 mRNA表达差异无统计学意义.结论 MLH1基因415G/C多态可能是我国散发结肠癌的遗传易感因素,但不是通过下调MLH1 mRNA表达而致病的.结肠癌家系中C等位基因携带者患结肠癌可能性更大.