Functional polymorphisms in FAS and FASL contribute to risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population

Accumulating evidences indicate that the functional FAS− 1377G > A, − 670A > G and FASL− 844T > C polymorphisms affect the risk of several kinds of cancers. However, their roles in the development of larynx and hypopharynx squamous cell carcinoma (SCC) were still unknown in the Chinese. In the current study, we examined whether these functional genetic variants were associated with the risk of larynx and hypopharynx squamous SCC in a Han Chinese population. The FAS and FASL polymorphisms were genotyped in 300 patients with laryngeal and hypopharyngeal SCC and 300 control subjects by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis revealed that subjects carrying the FASL–844CT or TT genotype had a significantly decreased risk of developing laryngeal and hypopharyngeal SCC [odds ratio (OR) = 0.69; 95% confidence interval (CI) = 0.51–0.93; P = 0.016; or, OR = 0.41; 95% CI = 0.20–0.86; P = 0.009] compared with those carrying the CC genotype. Joint gene-smoking and gene-drinking effects were also observed, with the OR of CC genotype for smokers or drinkers were 5.15 (95%CI = 3.24–8.97) or 12.52 (95%CI = 7.31–22.47), respectively. Therefore, the FASL− 844T > C polymorphism is associated with genetic susceptibility of developing laryngeal and hypopharyngeal SCC in a Han Chinese population.     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.     

Association of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant with bipolar disorder

Here we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with bipolar disorder in a case–control study of 95 bipolar disorder patients and 201 healthy controls (χ² = 13.382, P = 0.001). With the polymerase chain reaction restriction fragment length polymorphism method we developed we were able to show the association for the first time. This new finding may provide evidence to understand the mechanism of the disease.     

Association between the − 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: A systematic review and meta-analysis

Background

A variety of studies have evaluated the association between the − 786T>C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease (CAD). However, the results remain conflicting. To better understand the role of eNOS − 786T>C polymorphism in CAD risk, we conducted a comprehensive systematic review and meta-analysis.

Methods

Case–control, cohort or cross-sectional studies evaluating the association between eNOS − 786T>C polymorphism and CAD risk were searched in electronic databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (up to January 2013). Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between eNOS − 786T>C polymorphism and CAD risk. Statistical analysis was performed with Review Manager 5.0 and STATA12.0.

Results

Twenty-four studies were analyzed between 6192 CAD cases and 9281 healthy controls. The combined results of overall analysis showed significant positive associations between CAD risk and eNOS − 786T>C polymorphism in dominant model (OR = 1.45, 95% CI = 1.27–1.65), recessive model (OR = 1.37, 95% CI = 1.20–1.56), homozygote comparison (OR = 1.64, 95% CI = 1.31–2.04), heterozygote comparison (TC vs. TT, OR = 1.39, 95% CI = 1.23–1.57; CC vs. TC, OR = 1.20, 95% CI = 1.04–1.37) and allele comparison (OR = 1.35, 95% CI = 1.21–1.50). On subgroup analysis based on the ethnicity of population (Caucasians, Asians and others), significant differences were found in all genetic models for Caucasians, similar associations existed in Asians except heterozygote comparison (CC vs. TC). However, the associations were only found in dominant model, heterozygote comparison (TC vs. TT) and allele comparison for the populations named others.

Conclusions

Our investigations demonstrate the significant associations between eNOS − 786C>T polymorphism and CAD risk, and this polymorphism might become an early marker for the risk evaluation of CAD.     

FoxP3 genetic variants and risk of non-small cell lung cancer in the Chinese Han population

CD4⁺CD25⁺ regulatory T cell-mediated immunosuppression is one of the crucial mechanisms that tumor cells use to evade the immune system. The forkhead box P3 (FoxP3) gene regulates regulatory T-cell development and function and may modulate the susceptibility to non-small cell lung cancer (NSCLC). Because a single nucleotide polymorphism (SNP) within the FoxP3 gene (rs3761548 in the promoter region) is associated with susceptibility to Graves' disease, this study detected rs3761548 in a hospital-based case–control study. A total of 192 NSCLC patients and 259 healthy subjects were recruited for the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis of FoxP3 SNP. The data showed that the A allele of rs3761548 significantly increased NSCLC risk (P = 0.000, OR = 2.32, 95%CI = 1.736–3.102). The AC genotype, AA genotype, and the combined A variant genotype (AA + AC) were also associated with a higher risk of NSCLC (OR [95%CI] = 2.147[1.419–3.247], 4.413[2.359–8.255], and 2.563[1.746–3.761], respectively). Moreover, a significantly higher frequency of AA + AC genotype was observed in patients with stage II NSCLC (OR, 2.053; 95%CI, 1.033–4.078). In conclusion, the data from the current study demonstrated for the first time the association of the FoxP3 SNP with a risk of developing NSCLC in the Chinese Han population.     

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: A meta-analysis

Purpose

Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case–control studies. To clarify these associations, we conducted a meta-analysis.

Methods

We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association.

Results

There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR = 1.14, 95%CI = 1.03–1.26, P = 0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR = 0.63, 95%CI = 0.46–0.88, P = 0.0006; recessive, OR = 0.61, 95%CI = 0.38–0.99, P = 0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR = 0.38, 95%CI = 0.19–0.75, P = 0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models.

Conclusions

MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found thatMMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.     

Association of IL-12, IL-18 variants and serum IL-18 with bladder cancer susceptibility in North Indian population

IL-12 and IL-18 are immunomodulatory cytokines that play important roles in host immune response against cancers. Variation in DNA sequence in gene promoter may lead to altered IL-18 production and/or activity, and hence can modulate an individual's susceptibility to BC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter −137 G/C and −607C/A polymorphisms and IL12 (− 16974) A/C with the risk of BC in North Indian population. Polymorphisms in IL-18 and IL-12 genes were analyzed in 200 BC patients and 200 age, ethnicity and sex-matched controls, using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) and amplification refractory mutation specific-polymerase chain reaction (ARMS) method. The concentrations of IL-18 in serum were determined by ELISA. Significant association was observed with IL18 (− 137) G/C heterozygous genotype (GC) with 1.96 folds risk of BC as well at C allele carrier and variant C allele having 2 fold and 1.6 fold risk for BC respectively. IL18 (− 607) C/A, heterozygous CA genotype also showed a high risk (OR = 1.59) for BC. While IL12 (− 16974) A/C heterozygote genotype and C allele carrier demonstrated reduced risk of BC. Hetero genotype of IL18 (− 137) G/C was associated with risk of recurrence (HR = 2.35) in superficial BC patients receiving BCG treatment thus showing least survival. The distributions of IL-18 gene haplotypes were not significantly different between patients and controls. Serum IL-18 levels were significantly higher in BC patients than in the healthy subjects (p = 0.025). Serum IL-18 levels was also significantly associated with IL18 (− 137) G/C in heterozygous genotype (GC) (p = 0.048). Our results suggest that IL-18 gene polymorphism contributes to bladder cancer risk whereas IL-12 is protective. A relation between IL18 (− 137) G/C in heterozygous genotype with elevated IL-18 serum level and bladder cancer risk has been registered in the present study.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

Association of TGF-β1 − 509 C/T, 29 C/T and 788 C/T gene polymorphisms with chronic periodontitis: A case–control study

The aim of this study was to investigate the possible association between TGF-β1 − 509 C/T (rs1800469), 29 C/T (Prol10Leu, rs1800470) and 788 C/T (Thr263Ile, rs1800472) gene polymorphisms and chronic periodontitis (CP) in a sample of Iranian population. This case–control study was conducted on 100 CP patients and 100 healthy unrelated, age-, sex-, and ethnicity-matched. Genotyping was performed by tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. Our findings showed that there was a significant difference between the groups regarding TGF-β1 29 C/T (rs1800470) polymorphism (χ2 = 23.23, P < 0.0001). The CT and TT genotypes increased the risk of CP in comparison with the CC genotype (OR = 4.42, 95% CI = 2.16–9.06, P < 0.001 and OR = 5.84, 95% CI = 2.32–14.71, P < 0.001, respectively). The T allele increased the risk of CP (OR = 2.50, 95% CI = 1.66–3.74, P < 0.001) in comparison with C allele. No significant association was found among the groups regarding − 509 C/T and 788 C/T variants of TGF-β1 gene. This study shows that TGF-β1 29 C/T polymorphism, but not − 509 C/T and 788 C/T polymorphisms, may contribute to the development of CP in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are needed to validate our findings.     

DCC (deleted in colorectal carcinoma) gene variants confer increased susceptibility to gallbladder cancer (Ref. No.: Gene-D-12-01446)

Background and aim

GBC is a lethal and multifaceted disease. Deleted in colorectal carcinoma (DCC) is a well known tumor suppressor gene. Recently a small genome-wide association study (GWAS) identified DCC to be significantly associated with gallbladder cancer (GBC) susceptibility in a Japanese population sample. However, the study sample size was small and lacked independent replication. Therefore, the present study was carried out to replicate the association of two GWAS identified DCC SNPs (A>G_rs4078288, C>T_rs7504990) and two other SNPs (C>G_rs2229080 and A>G_rs714) previously associated with various cancers.

Methodology

The study was accomplished in 406 GBC cases and 260 healthy control samples from North India. Genotyping was carried out by PCR-RFLP and Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16 and functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP).

Result

We did not observe association with GWAS-identified SNPs of DCC but other SNPs showed significant association. In addition, a DCC haplotype G_rs2229080-A_rs4078288-C_rs7504990-A_rs714 conferred high risk of GBC in India. The haplotype associated risk was independent of gallstone, sex or tobacco usages which are well-known modifiers of GBC risk. Further analysis suggested DCC A>G_rs714 as a major risk conferring SNP in the Indian population.

Conclusion

This study re-affirms the role of plausible tumor suppressor DCC variants, in gallbladder carcinogenesis and the risk haplotype may be explored as a useful marker for GBC susceptibility.     

ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma

The EGF (epidermal growth factor) receptor-tyrosine kinase inhibitor ZD1839 (Gefitinib, 'Iressa') blocks the cell signaling pathways involved in cell proliferation, survival, and angiogenesis in various cancer cells. TNF-related death apoptosis inducing ligand (TRAIL) acts as an anticancer agent. We investigated the antitumor effects of ZD1839 alone or in combination with TRAIL against human esophageal squamous cell cancer (ESCC) lines. Although all ESCC cells expressed EGF receptor at a protein level, the effect of ZD1839 on cell growth did not correlate with the level of EGFR expression and phosphorylation of EGF receptor protein in ESCC lines. ZD1839 caused a dose-dependent growth arrest at G0-G1 phase associated with increased p27 expression. As TE8 cells are resistant to TRAIL, we tested whether ZD1839 combined with TRAIL induced apoptosis of TE8 cells via the inhibition of EGF receptor signaling by ZD1839. ZD1839 inhibited the phosphorylation of Akt, and enhanced TRAIL-induced apoptosis via activation of caspase-3 and caspase-9, and inactivation of Bcl-xL. Our results indicated that ZD1839 has anti-cancer properties against human esophageal cancer cells. ZD1839 also augmented the anti-cancer activity of TRAIL, even in TRAIL-resistant tumors. These results suggest that treatment with ZD1839 and TRAIL may have potential in the treatment of ESCC patients.     

A genetic variant in the promoter of APE1 gene (− 656 T > G) is associated with breast cancer risk and progression in a Chinese population

Background/aims

APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (− 656 T > G and 1349 T>G) and breast cancer risk.

Methods

We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results

We found that the variant genotypes of the − 656 T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.56–0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (< 52 years) (OR = 0.65, 95% CI = 0.46–0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P = 0.020, OR = 0.64, 95% CI = 0.44–0.94). We did not observe any significant association between the 1349 T>G polymorphism and breast cancer risk.

Conclusion

Our results suggest that the APE1 − 656 T>G but not the 1349 T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.     

The genetic polymorphisms of cathepsin S were associated with metabolic disorders in a Chinese Han population

Cathepsin S (CTSS) played an important role in the etiology of cardiovascular disease and metabolic syndrome. Few studies had been reported on the association between the polymorphisms of CTSS and metabolic disorders in Asian population. Therefore we explored the association between the polymorphisms of CTSS and metabolic disorders in a Chinese Han population. The subjects were a Chinese Han cohort with 1160 participants, and the genotyping was performed with PCR-RFLP. Polymorphism rs16827671 was associated with BMI and serum total cholesterol (P = 0.001; P = 0.02, respectively). Subjects with CT genotype of rs16827671 had a higher risk of hypercholesterolemia (OR = 1.64, 95% CI: 1.15–2.33, P = 0.006) compared with TT genotype. Subjects with AG genotype of rs11576175 had lower risks of hypertriglyceridemia and borderline hypercholesterolemia (OR = 0.52, 95% CI: 0.36–0.73, P = 0.0001; OR = 0.52, 95% CI: 0.35–0.77, P = 0.001, respectively) compared with GG genotype. Compared with the haplotype TG, haplotype TA had a lower risk of hypertriglyceridemia and a higher risk of borderline hypercholesterolemia (OR = 0.62, 95% CI: 0.44–0.88, P = 0.002; OR = 1.59, 95% CI: 1.10–2.31, P = 0.008, respectively), and haplotype CA had a lower risk of hypercholesterolemia (OR = 0.35, 95% CI: 0.18–0.68, P = 0.002). In conclusion, we found that the genetic polymorphisms of CTSS were associated with metabolic disorders in a Chinese Han population, which would enrich the knowledge on genetic mechanisms of the pathogenesis of metabolic disorders.     

Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with type 1 diabetes mellitus: A meta-analysis

To evaluate the association between costimulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus(T1DM), sixty-three published studies before December, 2011 were included. Meta-analysis was performed for each genotype in a random/fixed effect model. The combined odds ratio (OR) with 95% confidence interval (95%CI) was calculated to estimate the strength of the association. Overall, significant correlation was noted between CTLA-4 gene polymorphism (i.e. +49A/G, CT60A/G in a per-allele model) and the risk of T1DM (for +49A/G: OR=1.47, 95%CI=1.36-1.60, P<0.001; for CT60A/G: OR=1.31, 95%CI=1.18-1.45, P<0.001). However, no significant association was noted between C(-318)T polymorphism and T1DM. In the subgroup analysis, for +49A/G and CT60A/G, the statistically significant associations were also demonstrated in diverse racial descents (Caucasian and Asian) and age of onset (<20years and >20years). In conclusion, our results suggest that CTLA-4 polymorphism contributes to the susceptibility of T1DM.     

Vascular endothelial growth factor polymorphisms and risk of Alzheimer's disease: A meta-analysis

There were conflicting results about whether promoter polymorphisms (− 2578C/A, − 1154G/A) of vascular endothelial growth factor (VEGF) gene is a risk factor of Alzheimer's disease (AD). To determine the relationship between them, a meta-analysis is needed urgently. We searched all the reports about VEGF promoter polymorphisms (− 2578C/A, − 1154G/A) and AD risk from PubMed, Web of Science, Cochrane Collaboration and Google Scholar database for the period up to 1 August, 2012. A total of 7 studies were included in this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated applying fixed or random effects models. There was no significant association between VEGF − 2578C/A polymorphisms and AD risk in all gene models (OR = 1.08, 95% CI = 0.94–1.23 for A vs. C; OR = 1.19, 95% CI = 0.89–1.59 for AA vs. CC; OR = 1.15, 95% CI = 0.91–1.45 for AA vs. CC + CA; OR = 1.11, 95% CI = 0.98–1.25 for AA + CA vs. CC). Similar results were provided in subgroup analysis by ethnicity. For the VEGF − 1154G/A polymorphisms, lack of an association was also found (A vs. G: OR = 0.89, 95% CI = 0.79–1.01; AA vs. GG: OR = 0.82, 95% CI = 0.62–1.08; AA vs. GA + GG: OR = 0.89, 95% CI = 0.68–1.16; AA + AG vs. GG: OR = 0.85, 95% CI = 0.72–1.00). Conclusively, the result of this meta-analysis suggested that VEGF promoter polymorphisms (− 2578C/A, − 1154G/A) might not contribute to the susceptibility of AD.     

Identification of the up-regulation of TP-alpha, collagen alpha-1(VI) chain, and S100A9 in esophageal squamous cell carcinoma by a proteomic method

Esophageal squamous cell carcinoma (ESCC) is one of the most common primary malignant tumor of digestive tract. However, the early diagnosis and molecular mechanisms that underlie tumor formation and progression have been progressed less. To identify new biomarkers for ESCC, we performed a comparative proteomic research. Isobaric tags for relative and absolute quantitation-based proteomic method was used to screen biomarkers between ESCC and normal. 802 non-redundant proteins were identified, 39 of which were differentially expressed with 1.5-fold difference (29 up-regulated and 10 down-regulated). Through Swiss-Prot and GO database, the location and function of differential proteins were analyzed, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc. Among the differentially expressed proteins, TP-alpha, collagen alpha-1(VI) chain and S100A9 were verified to be upregulated in 77.19%, 75.44% and 59.65% of ESCC by immunohistochemistry and western-blot. Diagnostic value of these three proteins was validated. These results provide new insights into ESCC biology and potential diagnostic and therapeutic biomarkers, which suggest that TP-alpha, collagen alpha-1(VI) chain and S100A9 are potential biomarkers of ESCC, and may play an important role in tumorigenesis and development of ESCC.     

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population

The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.     

Polymorphisms in the IL-18 and IL-12B genes and their association with the clinical outcome in Croatian patients with Type 1 diabetes

Genetic variants of IL-18 and IL-12B may be important in immunoregulatory abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM), that contribute to individual differences in response to a treatment. Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease.