Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease.

BACKGROUND: Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. RESULTS: Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively. CONCLUSIONS: In conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

[The effects of DNA methylation on the homeostasis in vascular diseases].

Homeostasis is fundamental to maintain normal physiological functions in our body. Internal and external physical, chemical and biologial changes can cause dysregulation of vascular homeostasis, which is closely associated with the homeostasis of oxygen supply, blood transportation and lipid metabolism. Subsequent epigenetic modifications are able to lead to abnormal structures and function of vessels. DNA methylation has been shown to play a vital role in the development of vascular diseases. In addition, 5-hydroxymethylcytosine (5hmC) and N(6)-methyladenine (m(6)A), as new epigenetic modifications, provide additional clues for vascular diseases. In this review, we summarize the effects of DNA methylation on the homeostasis dysregulation in the vascular diseases.

Association of CDKN2BAS polymorphism rs4977574 with coronary heart disease: a case-control study and a meta-analysis.

The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p=0.002; allele: p=0.002, odd ratio (OR)=1.57, 95% confidential interval (CI)=1.18-2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females (χ2=10.29, p=0.003, OR=2.14, 95% CI=1.31-2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: χ2=14.64, degrees of freedom (df)=2, p=0.0002; allele: χ2=11.31, df=1, p=0.0008, OR=1.87, 95% CI=1.30-2.70). Similar observation was also found in males younger than 65 years (genotype: χ2=8.63, df=2, p=0.04; allele: χ2=7.55, df=1, p=0.006, OR=1.45, 95% CI=1.11-1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p<0.0001, OR=1.27, 95% CI=1.22-1.31).

Impact of gender and age on the association of the BUD13-ZNF259 rs964184 polymorphism with coronary heart disease.

OBJECTIVE: Coronary heart disease (CHD) is the most common cause of death worldwide. This study aimed to validate the association of the rs964184 polymorphism with the CHD risk and included 874 CHD patients and 776 controls. METHODS: rs964184 polymorphism genotyping was performed using Tm-shift polymerase chain reaction. RESULTS: A strong association of the rs964184 polymorphism with CHD was found (genotype: X2=14.365, p=0.001; allele: X2=14.191, p=1.67x10-4; power=0.965). Gender analysis revealed a significant association only in males (genotype: X2=12.387, p=0.002; allele: X2=12.404, p=4.32x10-4; OR=1.467, 95% CI=1.185-1.817, power=0.945). Age and gender analyses revealed significant associations of the rs964184 polymorphism with CHD in males between the ages of 55 and 65 years (genotype: X2=10.070, p=0.007; allele: X2=10.077, p=0.002; OR=1.706, 95% CI=1.224-2.377, power=0.996) and in females older than 65 years (genotype: X2=9.462, p=0.009; allele: X2=9.560, p=0.002; OR=2.112, 95% CI=1.308-3.412, power=0.994). Further subgroup analysis suggested that rs964184 genotypes were significantly associated with TG levels in the patients (r=0.191, adjusted p=1.05x10-5) and controls (r=0.101, adjusted p=0.026). CONCLUSION: Our results indicate that both gender and age have great impacts on the association of the rs964184 polymorphism with CHD among Chinese.

CDKN2A and CDKN2B methylation in coronary heart disease cases and controls.

The aim of the present study was to investigate the association between cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) methylation, and coronary heart disease (CHD), and to explore the interaction between methylation status and CHD clinical characteristics in Han Chinese patients. A total of 189 CHD (96 males, 93 females) and 190 well-matched non-CHD controls (96 males, 94 females) were recruited for the study. Methylation-specific polymerase chain reaction technology was used to examine gene promoter methylation status. Comparisons of methylation frequencies between CHD and non-CHD patients were carried out using the Chi-square test. Methylation levels of CDKN2A and CDKN2B genes were not found to be associated with the risk of CHD. However, the mean age of CDKN2A-hypermethylated participants was significantly lower than CDKN2A-unmethylated participants (58.73±5.88 vs. 62.62±5.36 years, adjusted P<0.001). Conversely, the mean age of CDKN2B-hypermethylated participants was significantly higher compared with CDKN2B-unmethylated participants (62.26±5.48 vs. 58.33±7.47 years, adjusted P=0.048). In addition, CDKN2B methylation frequencies were significantly increased in female participants compared with males (99.47 vs. 11.98%, P=0.032). In conclusion, the results indicated that CDKN2A and CDKN2B promoter methylation frequencies were significantly associated with age, and there was a gender dimorphism in CDKN2B methylation.

Chemotherapy-induced hypomethylation of N-myc downstream-regulated gene 4 in the bone marrow of patients with acute myeloid leukemia.

N-myc downstream-regulated gene 4 (NDRG4) has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced NDRG4 changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the NDRG4 gene were measured using bisulfite pyrosequencing techniques. The results indicated significantly reduced gene-body methylation levels of NDRG4 during chemotherapy (prior to chemotherapy: 9.35±4.22%; following chemotherapy: 7.54±3.11%; P=0.030). Further analysis of AML subtypes revealed the methylation reductions were principally contributed by patients with M2 subtype AML (prior to chemotherapy: 9.91±4.76%; following chemotherapy: 5.26±1.16%; P=0.038). A significant association was also observed between the patient age and the altered levels of NDRG4 gene-body methylation in patients with M2 subtype AML (r=0.761; P=0.047), suggesting that reductions in induced-methylation may be age-dependent in patients with M2 subtype AML during chemotherapy. Therefore, age may affect the induced methylation levels of NDRG4 gene-body in patients with AML (particularly patients with M2 subtype AML) during chemotherapy.

TGFB2 and BCL2L11 methylation in male laryngeal cancer patients.

DNA methylation is a major regulatory mechanism of gene expression. The aim of the present study was to test the association of transforming growth factor ß2 (TGFB2) and B cell lymphoma 2-like 11 (BCL2L11) gene methylation with the risk of laryngeal squamous cell carcinoma (LSCC). Using bisulfite pyrosequencing technology, DNA methylation levels of TGFB2 promoter and BCL2L11 gene-body CpG cytosines were measured in 90 LSCC tissues and 90 adjacent normal tissues. Analysis of variance and paired sample t-test were used to determine the association of gene methylation and the risk of LSCC. Our results revealed that there were no differences in TGFB2 and BCL2L11 methylation levels between the LSCC tissues and the paired normal tissues (P>0.05). Further breakdown analyses demonstrated that the association results of the two gene methylation levels and LSCC remained unchanged with the age, smoking history, histological differentiation or clinical stage of the LSCC patients (all adjusted P>0.05). In conclusion, there is no association of TGFB2 promoter and BCL2L11 gene-body methylation with the risk of LSCC in males.

SSTR2 promoter hypermethylation is associated with the risk and progression of laryngeal squamous cell carcinoma in males.

BACKGROUND: Somatostatin receptor 2 (SSTR2) encodes somatostatin receptor that can inhibit the cell proliferation of solid tumors. Promoter hypermethylation is likely to silence the expression of SSTR2. The goal of our study was to investigate the association between SSTR2 promoter methylation and the risk and progression of laryngeal carcinoma. METHODS: In the current study, tumor tissues and their adjacent non-tumor tissues were collected from a total of 87 laryngeal squamous cell carcinoma (LSCC) male patients. DNA methylation levels of nine SSTR2 promoter CpGs were measured using the bisulphite pyrosequencing technology. RESULTS: Our results revealed that there was a significantly increased SSTR2 promoter methylation in LSCC tissues than in their adjacent non-cancerous tissues (adjusted P = 0.003). Breakdown analysis by age indicated that the significant association was mainly contributed by patients younger than 60 (adjusted P = 0.039) but not in patients older than 60. Meanwhile, the significant association was observed in the patients with moderately (adjusted P = 0.037) and well differentiated tissues (adjusted P = 0.028), as well as the patients with histological stage IV (adjusted P = 0.031). Multivariate Cox analysis suggested that SSTR2 promoter methylation was an independent prognostic factor of LSCC (HR = 1.127, 95 % CI = 1.034-1.228). CONCLUSIONS: In conclusion, SSTR2 promoter hypermethylation might be associated with the risk and progression of LSCC in males.

CDKN2B, SLC19A3 and DLEC1 promoter methylation alterations in the bone marrow of patients with acute myeloid leukemia during chemotherapy.

Previous studies have demonstrated that promoter hypermethylation of tumor suppressor genes contributes to the occurrence and development of acute myeloid leukemia (AML). However, the association of DNA methylation with chemotherapeutic outcomes remains unknown. In the present study, 15 patients with AML were recruited, and the promoter methylation status of cyclin-dependent kinase inhibitor 2B (CDKN2B), solute carrier family 19 member 3 (SLC19A3) and deleted in lung and esophageal cancer 1 (DLEC1) genes was examined prior to and following various chemotherapeutic regimens in order to identify any alterations. The results suggested that chemotherapy-induced hypermethylation of CDKN2B and DLEC1 may be specific to males and females, respectively, and that there were no alterations in SLC19A3 methylation following chemotherapy. These results may provide an improved understanding of gene methylation to guide the development of an individualized chemotherapy for AML. Due to the complexity of AML and the wide range of treatment types, future studies with a larger sample size are required in order to verify the results of the present investigation.

Elevated methylation of CMTM3 promoter in the male laryngeal squamous cell carcinoma patients.

OBJECTIVE: CKLF-like MARVEL transmembrane domain containing 3 (CMTM3), as a tumor suppressor gene, plays an important role in the suppression of cell growth and apoptosis. The goal of our study is to investigate the association between CMTM3 promoter methylation and laryngeal squamous cell carcinoma (LSCC). DESIGN AND METHODS: Using the bisulfite pyrosequencing technology, DNA methylation levels of seven CpG sites in CMTM3 promoter are measured in tumor tissues and their adjacent tissues of 76 male LSCC patients. RESULTS: Our results reveal a significantly elevated promoter methylation of CMTM3 in tumor tissues compared with their adjacent tissues (P<0.001). A breakdown analysis by age shows that significant association of CMTM3 promoter methylation with cancer risk is specific to the LSCC patients older than 55years (P<0.001) but not in the younger patients (P=0.305). Moreover, the association is only observed in the LSCC patients with smoking behavior (P=0.001). Breakdown analysis also shows that CMTM3 promoter methylation is associated with cancer risk among patients with stage I LSCC (P<0.001). CONCLUSION: In conclusion, our study indicates that elevated CMTM3 methylation is a risk factor in male LSCC patients, especially in the patients with age over 55years and with smoking behavior.

APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy.

Aberrant promoter DNA methylation is a major mechanism of leukemogenesis in hematologic malignancies, including acute myeloid leukemia (AML). However, the association between promoter methylation with chemotherapeutic outcomes remains unknown. In the present study, bone marrow samples were collected prior to and following chemotherapy in 30 AML patients. Methylation-specific polymerase chain reaction technology was used to examine the promoter methylation status of adenomatous polyposis col 2 (APC2) and cytochrome P450 family 1 subfamily B polypeptide 1 (CYP1B1). The results revealed no change in the methylation status of the APC2 promoter in patients following various chemotherapy regimens. However, the methylation status of the CYP1B1 promoter changed in response to 6 different chemotherapy regimens. AML patients of the M3 subtype displayed an induction of the CYP1B1 promoter methylation levels more frequently (57.1%) than patients affected by the other subtypes (M1: 33.3%; M2: 12.5%; M4: 16.7%; M5: 0% and M6: 0%). In addition, a higher frequency of male patients (4/13) exhibited modulation of the CYP1B1 promoter methylation status compared with female patients (3/17). Furthermore, of five AML patients with a poor prognosis, two exhibited changes leading to CYP1B1 hypomethylation and two leading to CYP1B1 hypermethylation. By contrast, three other patients exhibited hypermethylation changes along with remission. This may be explained by the different chemotherapy regimens used to treat these patients or by other unknown factors. The present study revealed that CYP1B1 promoter methylation was induced during chemotherapy, whereas the APC2 promoter remained hemimethylated. Furthermore, the changes in CYP1B1 methylation were dependent on the AML subtypes and the gender of the patients.

Association between the methylation status of the MGMT promoter in bone marrow specimens and chemotherapy outcomes of patients with acute myeloid leukemia.

The O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the MGMT promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone marrow specimens was determined by methylation-specific polymerase chain reaction. The results indicated that the methylation status of the MGMT promoter was influenced by different chemotherapeutic regimens. The MGMT methylation status of M4 patients (3 out of 6) were more chemosensitive, compared with that of patients with other AML subtypes (M1, 1 out of 3; M2, 0 out of 8; M3, 3 out of 7; M5, 0 out of 3; and M6, 1 out of 3). Age-based analysis revealed that the group aged ≤60 years (7 out of 24 patients) exhibited more methylation changes than patients aged >60 years (1 out of 6). Male patients (4 out of 13) were more susceptible to chemotherapy-induced methylation changes than female patients (4 out of 17). Thus, the methylation status of the MGMT promoter may serve as a potential biomarker to predict the therapeutic outcomes in male AML patients. However, further studies in larger sample sets are required to confirm the present findings.

Association of four CpG-SNPs in the vascular-related genes with coronary heart disease.

Vascular-related gene polymorphism can affect the susceptibility of coronary heart disease. In current study, we aimed to evaluate the contribution of four vascular-related gene CpG-SNPs to coronary heart disease (CHD). A total of 784 angiography-proven CHD patients and 746 non-CHD controls were included in the current association study. The four CpG-SNPs (including VEGFA rs1005230, ACE rs4316, CST3 rs3827143 and AGTR1 rs275653) were genotyped using the Sequenom MassARRAY platform. All genotype distribution of four SNPs met HWE. Among the four CpG-SNPs, none was found to be associated with CHD on both genotype and allele levels. Further subgroup tests by age or gender were unable to observe any significant associations of them with CHD. Our case-control study showed that none of four CpG-SNPs in the vascular-related genes was associated with the risk of CHD in Han Chinese, although we could not exclude other genetic variants of these vascular-related genes with contribution to CHD.

A lack of association between the IKZF2 rs12619285 polymorphism and coronary heart disease.

The IKZF2 rs12619285 polymorphism is associated with the eosinophil count, which has multidimensional functions in the pathogenesis of coronary heart disease (CHD). The aim of the present study was to investigate the contribution of the IKZF2 rs12619285 polymorphism to the risk of CHD in a Han Chinese population. In total, 721 CHD cases and 631 non-CHD controls were recruited for an association study of the IKZF2 rs12619285 polymorphism. Genotyping was performed using the melting temperature-shift polymerase chain reaction method. No statistically significant association was observed between the IKZF2 rs12619285 polymorphism and CHD (odds ratio, 1.139, 95% confidence interval, 0.927-1.334; P=0.17). In addition, subgroup analyses by gender or age were unable to identify any association between IKZF2 rs12619285 and CHD (P>0.05), and there was no significant correlation between IKZF2 rs12619285 and the severity of CHD (P>0.05). The power of the case-control study was determined to be 63.3%. In addition, the G allele frequency was calculated as 63.6% in the Han Chinese population, which was similar to the 59.3% recorded for the HapMap Chinese population of Han Chinese individuals living in Beijing, compared with 24.3% in European descendents (HapMap-CEU). Therefore, the results indicated that the IKZF2 rs12619285 polymorphism was not associated with CHD in a Han Chinese population. The discrepancy in the association between rs12619285 and CHD may be due to the ethnic differences between Han Chinese and European populations.

Association of seven thrombotic pathway gene CpG-SNPs with coronary heart disease.

OBJECTIVES: Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of this case-control study was to explore whether the CpG-SNPs of the thrombotic pathway genes contributed to the risk of CHD. METHODS AND MATERIALS: A total of 784 CHD patients and 738 healthy controls were recruited in the current association study, which evaluated 7 CpG-SNPs of the thrombotic pathway genes. The CpG-SNPs included THBS4 rs17878919, CYP2C19 rs12773342, P2RY12 rs1491974, ITGA2 rs26680, FGB rs2227389, F7 rs510317 and F5 rs2269648. SNP genotyping was performed with a Sequenom Mass Spectrometry Genetic Analyzer. RESULTS: Our results demonstrated that CYP2C19 rs12773342 polymorphism was significantly associated with CHD in the recessive model (χ(2)=5.41, df=1, P=0.020, OR=1.455, 95% CI=1.060-1.996). A breakdown analysis by age showed that the association of CYP2C19 rs12773342 with CHD was mainly found in individuals aged 55-65 (genotype: χ(2)=7.93, df=2, P=0.019; allele: χ(2)=4.45, df=1, P=0.035). In addition, we also observed a significant association between F7 rs510317 polymorphism and CHD in males (genotype: χ(2)=7.24, df=2, P=0.027). There was no significant association with CHD for the remaining CpG-SNPs. CONCLUSION: Our results supported that the CYP2C19 rs12773342 and F7 rs510317 polymorphisms were associated with CHD in the Han Chinese population.

PPARD rs2016520 polymorphism and circulating lipid levels connect with brain diseases in Han Chinese and suggest sex-dependent effects.

The PPARD polymorphisms were shown to be associated with circulating lipoprotein metabolism in various diseases. We aimed to check the contribution of PPARD rs2016520 and lipid concentration to the risk of intracerebral hemorrhages (ICH) and brain tumors (BT) in Han Chinese. A total of 864 participants were included in the case-control study. The melting temperature shift (Tm-shift) method was used for rs2016520 genotyping. Under the recessive model, PPARD rs2016520 was shown to be associated with the risk of ICH (P=0.029, odds ratio (OR)=2.72), specifically in males (P=0.045, OR=3.98). Additionally, we also found that the levels of TC and LDL-C were significantly higher in participants with brain diseases than in the controls (TC: P<0.0001; LDL-C: P<0.0001). Significantly higher HDL-C and lower ApoA-I levels were observed in the male patients with brain diseases (HDL-C: P<0.0001; ApoA-I: P=0.008), in contrast of a higher TG level in female ICH (P=0.023). Subsequent interaction analysis between PPARD rs2016520 and lipoprotein metabolism showed that the LDL-C level was positively correlated with ICH in the rs2016520-AA carriers (P<0.0001), but not in the other genotype carriers (AG or GG, P=0.300). Our results showed that PPARD rs2016520 displayed a strong relationship with ICH risk in the male Han Chinese. The TC and LDL-C levels were positively higher in the patients with brain diseases than in the controls. The levels of TG, HDL-C and ApoA-I were shown to affect brain disease in a gender-dependent model. The genotype rs2016520-AA showed significant interaction with the circulating LDL-C levels in ICH.

Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients.

Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.

Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart Disease: A Case-Control Study and Meta-Analysis.

OBJECTIVE: Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. METHODS: We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. RESULTS: Significant differences were observed between CHD cases and controls at the level of both genotype (χ2 = 8.964, df = 2, P = 0.011) and allele (χ2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088-1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). CONCLUSION: Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.

Association between six genetic polymorphisms and colorectal cancer: a meta-analysis.

OBJECTIVE: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). METHODS: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. RESULTS: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC (p=0.03, odds ratio [OR]=1.18, 95% confidence interval [CI]=1.01-1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC (p=0.004, OR=1.498, 95% CI=1.139-1.970), and this significant association is specific in Caucasians (p=0.004, OR=1.603, 95% CI=1.165-2.205). CONCLUSIONS: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC.

Investigation into the promoter DNA methylation of three genes (CAMK1D, CRY2 and CALM2) in the peripheral blood of patients with type 2 diabetes.

Promoter DNA methylation may reflect the interaction between genetic backgrounds and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). Calcium/calmodulin-dependent protein kinase 1D (CAMK1D), cryptochrome 2 (CRY2) and calmodulin 2 (CALM2) genes have been identified to be associated with a risk of T2D. Therefore, the aim of the present study was to investigate the contribution of promoter DNA methylation of these genes to the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of the CpG dinucleotides within the CAMK1D, CRY2 and CALM2 gene promoters were measured in 48 patients with T2D and 48 age- and gender-matched healthy controls. The results demonstrated that the promoters of these three genes were hypomethylated in the peripheral blood of all the subjects, and DNA methylation of these three genes did not contribute to the risk of T2D.