Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection

Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0–2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6–24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1–0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03–0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.     

Gene-gene interactions between interleukin-12A and interleukin-12B with the risk of brain tumor

Emerging evidence from preclinical and clinical studies has shown that interleukin-12 (IL-12) has some effectiveness against endogenously arising brain tumor. The aim of this study was to investigate interactions of IL-12A and IL-12B polymorphisms on the risk of brain tumor. We analyzed IL-12A rs2243115 and IL-12B rs3212227 polymorphisms in 170 patients with brain tumor and 222 healthy controls in a Chinese population using a polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing method. Individuals carrying a G allele of IL-12A rs2243115 had a significantly higher risk of developing brain tumor compared with those carrying a T allele (odds ratio [OR]=2.01, 95% confidence interval [CI], 1.17-3.45). After stratification analysis according to tumor types, a similarly higher risk was detected in patients with glioma (OR=2.56, 95% CI, 1.25-5.21). When gene-gene interactions were examined, carriers at both loci rs2243115 TG/GG and rs3212227 AC/CC had a 2.62-fold increased risk of glioma compared with those with rs2243115 TT and rs3212227 AC/CC genotypes (OR=2.62, 95% CI, 1.05-6.50). This study provides evidence that IL-12A rs2243115 may be associated with the risk of brain tumor. Additionally, gene-gene interactions of IL-12A rs2243115 and IL-12B rs3212227 may contribute to brain tumor susceptibility.     

Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis

IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case–control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95?% confidence intervals (95?% CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR?=?1.32, 95?% CI?=?1.06–1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR?=?1.34, 95?% CI?=?1.04–1.73; OR?=?2.03, 95?% CI?=?1.57–2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR?=?1.34, 95?% CI?=?1.00–1.80), Asian populations (OR?=?1.33, 95 % CI?=?1.06–1.67) and European populations (OR?=?1.54, 95 % CI?=?1.04–2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.     

Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure

Interleukin-1 (IL) plays a pivotal role in immune–inflammatory response that maintains periodontal homeostasis. A number of epidemiological studies have been conducted to investigate the associations between common polymorphisms of IL-1 (IL-1A, IL-1B) genes and risk of peri-implant disease, but the findings remain inconclusive. Thirteen studies evaluating the association between IL-1 polymorphisms and risk for peri-implant diseases (implant failure/loss, peri-implantitis) were included. Fixed model or random-effects models were applied to calculate overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) as risk estimates for IL-1 polymorphisms individually or in combination. Heterogeneity and publication bias were evaluated by Q-test, I ² statistic, Begg’s funnel plot and Egger’s test accordingly. The composite genotype of IL-1A (?889) and IL-1B (+3954) was associated with increased risk of implant failure/loss (OR 1.76, 95 % CI 1.21–2.57) and peri-implantitis (OR 2.34, 95 % CI 1.03–5.33). The significance was borderline in European descents (implant failure/loss: OR 1.48, 95 % CI 0.99–2.22; peri-implantitis: OR 1.65, 95 % CI 1.00–2.73). T allele of IL-1B (?511) was associated with increased risk of implant failure/loss (OR 1.28, 95 % CI 1.01–1.62), while the association was not significant in European descents (OR 1.12, 95 % CI 0.85–1.48). These findings support a potential role of IL-1 polymorphisms, particularly the composite genotype of IL-1A (?889) and IL-1B (+3954), in peri-implant disease susceptibility. More studies with large sample size are needed to validate the associations.     

Association Study of IL-12B Polymorphisms Susceptibility with Ankylosing Spondylitis in Mainland Han Population

Objective

This study aims to determine whether the genetic polymorphisms of IL-12B gene is a susceptibility factor to Ankylosing spondylitis (AS) in mainland Han Chinese population.

Method

Eight single-nucleotide polymorphisms (SNPs) (rs10045431, rs11167764, rs3212227, rs6556412, rs6556416, rs6871626, rs6887695 and rs7709212) in the IL-12B gene were genotyped by iMLDR Assay technology in 400 patients [96% (384/400) HLA-B27(+)] and 395 geographically and ethnically matched healthy controls in mainland Han Chinese population. The correlation between IL-12B genetic polymorphisms and AS activity index (BASDAI, BASFI) were tested.

Results

The significant difference was found in genotype distribution between AS and healthy controls (χ² = 6.942, P-value = 0.031) of the SNP rs6871626. Furthermore, significant evidence was also detected under the recessive model for minor allele A. The AA genotype carrier had 1.830 fold risk compared with C allele carrier (with CC and AC genotypes) [OR (95% CI) = 1.830 (1.131-2.961), P-value = 0.014]. Nevertheless, the difference was no longer significant after Bonferroni correction. Subset analysis on cases with HLA-B27(+) did find the same results. Three genotypic groups (AA, CC and CA) in rs6871626 site was highly associated with the BASDAI and BASFI (P-value = 0.012 and P-value = 0.023, respectively), after adjustment for effect of age, sex, and disease duration, the P-value was 0.031 and 0.041, respectively. The AA genotype of rs6871626 was also significantly correlated with an increased BASDAI and BASFI compared to the AC and CC genotypes in AS patients.

Conclusion

Our findings suggest that rs6871626 may be associated AS susceptibility and with disease activity (BASDAI, BASFI) in mainland Han Chinese population.     

IL12B and IL23R gene SNPs in Japanese psoriasis

Psoriasis is a common human skin disease whereby abnormal production of inflammatory mediators is believed to play an important role in its pathogenesis. The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12 and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23, were identified as psoriasis-susceptibility genetic factors in recent candidate gene and genome-wide association studies of Chinese and Europeans. Since there are significant differences in the incidence of psoriasis between Europeans and Japanese suggesting a genetic ethnic effect, we examined the association of IL12B and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560 controls and compared our results with those previously published for Europeans and Asians. Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR)?=?1.35, P?=?4.94E-04) and rs6887695 (OR?=?1.32, P?=?2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was found for the IL12B gene protective haplotype C-C (OR?=?0.71, P?=?1.84E-04) in Japanese, as previously elucidated in the studies of European ancestry.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.     

Association between polymorphisms in interleukin-4Rα and interleukin-13 and glioma risk: A meta-analysis

Introduction: It has been suggested that allergies are inversely associated with glioma risk. Single nucleotide polymorphisms in two allergy-related genes [interleukin (IL)-4Rα, IL-13] have been implicated in susceptibility to glioma; however, results from the published studies remained inconclusive. Methods: To derive a more precise relationship, we conducted a meta-analysis including seven case–control studies that investigated the influence of IL-4Rα rs1801275 and IL13 rs20541 polymorphisms on glioma risk. Data were extracted from these studies and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the strength of the association. Results: Overall, the pooled analysis showed that there was no significant association between the IL-4Rα rs1801275 polymorphism and glioma risk (OR = 0.99, 95%CI: 0.79–1.25, AG/GG vs. AA). However, we found that the IL13 rs20541 variant genotypes (GA/AA) were significantly associated with reduced risk for glioma (OR = 0.85, 95%CI: 0.75–0.97, GA/AA vs. GG). In the stratified analyses by ethnicity, marginally significant association between the IL13 rs20541 polymorphism and decreased glioma risk was found among Asian populations in dominant models (OR = 0.84, 95%CI: 0.70–1.00, GA/AA vs. GG). Conclusions: This meta-analysis suggests that the IL13 rs20541 but not the IL-4Rα rs1801275 polymorphism may be a genetic predictor for glioma. More studies with larger sample size are warranted to further elucidate the impact of the IL13 rs20541 polymorphism on glioma risk.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

IL-15 receptor alpha rs2228059 A>C polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Esophageal cancer is very aggressive; genetic polymorphisms may explain in part the individual differences in esophageal cancer susceptibility. We conducted a hospital based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin (IL)-15 and IL-15 receptor alpha (IL-15RA) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan^TM kit. The IL-15RA rs2228059 A>C polymorphism was associated with a decreased risk of ESCC in a recessive genetic model; However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated a significantly decreased risk of ESCC associated with the IL-15RA rs2228059 A>C polymorphism was evident among male, older, non-smoker, and non-drinker patients. These findings indicated that the functional polymorphism, IL-15RA rs2228059 A>C, might contribute to ESCC susceptibility. However, the statistical power of our study was limited because of the moderate sample size and absence of a validation cohort. Large well-designed studies are warranted to confirm our findings.     

Interleukin (IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population

Polymorphisms in Interleukin (IL)-21 have been researched in several cancers, but the association between IL-21 polymorphisms and thyroid cancer remains unclarified. This case–control study explored the role of five tagSNPs (rs12508721C > T, rs907715G > A, rs13143866G > A, rs2221903A > G and rs4833837A > G) in IL-21 gene in thyroid cancer development. IL-21 genotypes were examined in 615 thyroid cancer patients and 600 controls in Chinese population, and the associations with the risk of thyroid cancer were estimated by logistic regression. Moreover, the potential role of rs12508721C > T in thyroid cancer was further explored by biochemical assays. Compared with the rs12508721CC genotype, CT genotype presented a significantly decreased risk of thyroid cancer (adjusted odds ratios [OR] = 0.72; 95%CI = 0.57–0.94), the TT carriers had a further decreased risk of thyroid cancer (OR = 0.56; 95%CI = 0.41–0.87). Furthermore, our quantitative real-time PCR and Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the presence of rs12508721T allele led to more IL-21 expression. However, no significant difference was found in genotype frequencies for other four sites between cases and controls. These findings suggested that rs12508721 polymorphism in IL-21 might be a genetic modifier for the development of thyroid cancer.     

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.     

Association of the interleukin 15 (IL-15) gene polymorphisms with the risk of developing ulcerative colitis in Mexican individuals

Interleukin 15 (IL-15) is a Th1-related cytokine that triggers inflammatory cell recruitment with implications for pathogenesis in ulcerative colitis. The IL-15 gene is located within a 35 kb region of the q28-31 locus of chromosome 4. In the present work, the role of IL-15 gene polymorphisms as susceptibility markers for UC was evaluated. Seven polymorphisms of IL-15 (rs3806798, rs10833, rs4956403, rs2254514, rs2857261, rs10519613, and rs1057972) were genotyped by 5′ exonuclease TaqMan genotyping assays in a group of 199 Mexican patients with UC and 698 Mexican Mestizo healthy unrelated individuals. UC patients and healthy controls showed similar distribution of the rs3806798, rs10833, rs4956403, rs2857261, rs10519613, and rs1057972 polymorphisms. The rs2254514 polymorphism was significantly associated with decreased risk of UC as compared to controls under both dominant and additive models (OR 0.62, P_dom = 0.014 and OR 0.65, P_add = 0.02). The rs2254514 CC genotype was associated with young age at diagnosis <40 years (P = 0.03; OR 3.67). Five polymorphisms (rs1051613, rs2254514, rs2857261, rs1057972, and rs10833) were in strong linkage disequilibrium and were included in six haplotypes: H1 (ACAAC), H2 (CCGTC), H3 (CTAAT), H4 (CCAAT), H5 (CTAAC), and H6 (CCAAC). UC patients showed an increased frequency of the H6 haplotype (P = 0.005; OR 3.2) and a decreased frequency of the H5 haplotype (P = 0.031; OR 0.40). These results suggest that the IL-15 rs2254514 polymorphism might have an important role in the development of UC in the Mexican population. We were able to distinguish one risk and one protective uncommon haplotype for the development of UC.     

Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ² test. Gene–gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL-6, TNF-α and IL-10 did not show any association. In double combination, IL-6 ?597 GA and TNF-α ?308 GG genotypes increased the risk up to 21 times and in triple combination IL-6 ?597 AA, TNF-α ?308 GG and IL-10 ?592 CA increased the risk of T2DM up to 314 times. In gene–gene interaction allele ‘A’ of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL-6, TNF-α and IL-10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM.     

Combinations of cytokine gene network polymorphic markers as potential predictors of myocardial infarction

With the intent to identify informative predictors of myocardial infarction (MI) development in an ethnically homogenous group of Russian men after MI (255 subjects) and in a corresponding control group (257 subjects), an analysis of genotype frequency distribution for polymorphic DNA markers (SNP) rs16944 (?511C>T, IL1B gene), rs1800796 (?572G>C, IL6 gene), rs1800872 (?592C>A, IL10 gene), rs3212227 (1159A>C, IL12B gene), rs1800629 (?308G>A, TNF), rs909253 (252A>G, LTA), rs767455 (36A>G, TNFRSF1A) was conducted. Using the Monte Carlo method and a Markov chain (APSampler), allele combinations associated both with decreased and increased MI risk were revealed. The most significant results were obtained for IL6*C/C (P = 3 × 10^?4, OR = 6.3 CI 2.37–16.75), LTA*A + IL6*G/G (FDR = 2.3 × 10^?4, OR = 0.25 CI 0.14–0.46), LTA*G/G + IL12B*A/A (FDR = 0.0053, OR = 4.92 CI 1.8–13.33), TNF*G + LTA*G/G + TNFRSF1A*A (FDR = 0.013, OR = 4.38, CI 1.6–12.01), TNFRSF1A*G + IL10*A/A + IL12B*C (FDR = 0.016, OR = 8.79, CI 2.17–35.63), TNF*G + LTA*G/G + IL10*C (FDR = 0.0105, OR = 3.54 CI 1.55–8.09).     

Lack of association between the G+2044A polymorphism of interleukin-13 gene and chronic obstructive pulmonary disease: a meta-analysis

Numerous studies have investigated association of interleukin-13 (IL-13) G+2044A polymorphism with COPD susceptibility; however, the results were inconsistent and inconclusive. To evaluate the association between the IL-13 G+2044A polymorphism and susceptibility to COPD, a meta-analysis of published case–control studies was performed. Based on PubMed and Chinese database, this research selected studies that examined the association of the IL-13 G+2044A polymorphism with COPD. A genetic model-free approach was used to assess whether the combined data showed this association. Then a subgroup analysis was also performed, with stratifications for race, study design, and sample size. Six studies (total 1,213 COPD patients and 801 control subjects) for the IL-13 G+2044A polymorphism with COPD were included in the meta-analysis (G- vs A-allele: OR 1.12, 95 % CI 0.96–1.32, P = 0.15; genotypes GG+GA vs genotype AA: OR 0.99, 95 % CI 0.49–2.00, P = 0.98; genotype GG vs genotypes GA+AA: OR 1.18, 95 % CI 0.97–1.44, P = 0.09; genotype GA vs genotypes GG+AA: OR 0.85, 95 % CI 0.70–1.04, P = 0.11). This meta-analysis demonstrates that the IL-13 G+2044A polymorphism does not confer susceptibility to COPD. More detailed data about individual and environment, larger sample sizes with unbiased genotyping methods and matched controls in different populations are required.     

Case–control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A,SCN2A,SCN3A,SCN1B,and SCN2B and epilepsy

High-frequency action potentials are mediated by voltage-gated sodium channels, composed of one large α subunit and two small β subunits, encoded mainly by SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B genes in the brain. These play a key role in epilepsy, with the most commonly mutated gene in epilepsy being SCN1A. We examined whether polymorphisms in the above genes affect epilepsy risk in 1,529 epilepsy patients and 1,935 controls from four ethnicities or locations: Malay, Indian, and Chinese, all from Malaysia, and Chinese from Hong Kong. Of patients, 19 % were idiopathic, 42 % symptomatic, and 40 % cryptogenic. We genotyped 43 polymorphisms: 27 in Hong Kong, 28 in Malaysia, and 12 in both locations. The strongest association with epilepsy was rs3812718, or SCN1A IVS5N+5G>A: odds ratio (OR) = 0.85 for allele G (p = 0.0009) and 0.73 for genotype GG versus AA (p = 0.003). The OR was between 0.76 and 0.87 for all ethnicities. Meta-analysis confirmed the association (OR = 0.81 and p = 0.002 for G, and OR = 0.67 and p = 0.007 for GG versus AA), which appeared particularly strong for Indians and for febrile seizures. Allele G affects splicing and speeds recovery from inactivation. Since SCN1A is preferentially expressed in inhibitory neurons, G may decrease epilepsy risk. SCN1A rs10188577 displayed OR = 1.20 for allele C (p = 0.003); SCN2A rs12467383 had OR = 1.16 for allele A (p = 0.01), and displayed linkage disequilibrium with rs2082366 (r ² = 0.67), whose genotypes tended toward association with SCN2A brain expression (p = 0.10). SCN1A rs2298771 was associated in Indians (OR = 0.56, p = 0.005) and SCN2B rs602594 with idiopathic epilepsy (OR = 0.62, p = 0.002). Therefore, sodium channel polymorphisms are associated with epilepsy.     

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.