Heterogeneous Co-dominant Model Research Articles

Genetic scores of smoking behaviour in a Chinese population.

This study sought to structure a genetic score for smoking behaviour in a Chinese population. Single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were evaluated in a community-representative sample (N = 3,553) of Beijing, China. The candidate SNPs were tested in four genetic models (dominance model, recessive model, heterogeneous codominant model and additive model), and 7 SNPs were selected to structure a genetic score. A total of 3,553 participants (1,477 males and 2,076 females) completed the survey. Using the unweighted score, we found that participants with a high genetic score had a 34% higher risk of trying smoking and a 43% higher risk of SI at ≤18 years of age after adjusting for age, gender, education, occupation, ethnicity, body mass index (BMI) and sports activity time. The unweighted genetic scores were chosen to best extrapolate and understand these results. Importantly, genetic score was significantly associated with smoking behaviour (smoking status and SI at ≤18 years of age). These results have the potential to guide relevant health education for individuals with high genetic scores and promote the process of smoking control to improve the health of the population.

Association between miR-137 polymorphism and risk of schizophrenia: a meta-analysis.

miR-137, a brain-enriched microRNA, is involved in the control of neuronal proliferation, differentiation, and dendritic arborization, all of which are important for proper neurogenesis and relevant to schizophrenia. miR-137 is also known to regulate many genes implicated in schizophrenia risk. Although reports have associated the miR-137 polymorphism rs1625579 with this disease, their results have been inconsistent. The aim of this meta-analysis was to evaluate the relationship between rs1625579 and schizophrenia. Data were obtained from an electronic database, and pooled odds ratios (ORs) with 95% confidence intervals (95%CI) were used to test the association using the RevMan 5.3 software. Twelve case-control studies comprising 11,583 cases and 14,315 controls were included. An estimated lambda value of 0.46 was recorded, suggesting that a codominant model of inheritance was most likely. A statistically significant association was established under allelic (T vs G: OR = 1.15, 95%CI = 1.10-1.21, P < 0.001) and homogeneous codominant models (TT vs GG: OR = 1.32, 95%CI = 1.13-1.54, P < 0.001), but no such relationship was detected using the heterogeneous codominant model (GT vs GG: OR = 1.14, 95%CI = 0.97-1.34, P = 0.11). This meta-analysis demonstrates that the rs1625579 miR-137 genetic variant significantly increases schizophrenia risk.

Lack of association between a functional polymorphism (rs1800796) in the interleukin-6 gene promoter and lung cancer.

BackgroundA number of studies have examined the association between interleukin-6 (IL-6) rs1800796 polymorphism and risk of lung cancer but revealed inconsistent results. The aim of this study was to clarify the association between IL-6 rs1800796 polymorphism and risk of lung cancer.MethodsLiterature databases including PubMed, Embase and CNKI were searched up to January 2014. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) under co-dominant model, dominant model and recessive model were estimated using random-effects model.ResultsA total of seven studies, including 2691 lung cancer cases and 3067 controls, were included in the meta-analysis. The results suggested that IL-6 rs1800796 polymorphism was not associated with risk of lung cancer under homogeneous co-dominant model (OR = 1.06, 95%CI = 0.73-1.54), heterogeneous co-dominant model (OR = 1.24, 95%CI = 0.96-1.60), dominant model (OR = 1.23, 95%CI = 0.95-1.58) and recessive model (OR = 0.96, 95%CI = 0.70-1.32). The association was still not significant in either never-smokers (OR = 1.19, 95%CI = 0.95-1.48) or ever-smokers (OR = 1.73, 95%CI = 0.89-3.36).ConclusionThe present meta-analysis suggested that there was no association between IL-6 rs1800796 polymorphism and lung cancer, which was independent of smoking status.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060061508127855

Association between estrogen receptor alpha PvuII polymorphism and prostate cancer risk

Accumulating evidence has suggested that estrogen receptor alpha (ER-α) PvuII polymorphism might be involved in the development of prostate cancer (PCa). However, the results have been inconsistent. We therefore performed a meta-analysis to clarify the associations between ER-α PvuII polymorphism and PCa. A comprehensive search was conducted to identify all case-control studies of ER-α PvuII polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. A total of 14 studies were found to be eligible for meta-analyses of PvuII variant. Results from this study showed that ER-α PvuII polymorphism were significantly associated with PCa risk under all genetic models in overall population (homogeneous codominant model, OR = 1.57, 95% CI = 1.11-2.21, P = 0.010; heterogeneous codominant model, OR = 1.37, 95% CI = 1.06-1.77, P = 0.02; recessive model, OR = 1.27, 95% CI = 1.02-1.57, P = 0.03; dominant model, OR = 1.40, 95% CI = 1.09-1.79, P = 0.009; and allelic model, OR = 1.25, 95% CI = 1.06-1.48, P = 0.010). Further sensitivity analysis confirmed the significant association. In subgroup analyses stratified by PCa type, there was a significant association between PvuII polymorphism and sporadic PCa risk under both Caucasians and Asians. The meta-analysis indicated elected PvuII polymorphism of ER-α was a risk factor for PCa development.

The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson’s disease

The angiotensin-converting enzyme (ACE) may be involved in the pathogenesis of Parkinson's disease (PD). There have been several studies investigating the association between ACE gene I/D polymorphism and PD risk, but they reported inconsistent findings. We performed a meta-analysis to investigate the association between ACE gene I/D polymorphism and PD risk. Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models based on between-study heterogeneity. A total of five studies including 606 cases and 708 controls were finally included in the meta-analysis. Meta-analysis showed that there was no obvious association between ACE gene I/D polymorphism and PD risk under the homogeneous co-dominant model (OR = 1.14, 95% CI = 0.71-1.82), heterogeneous co-dominant model (OR = 0.92, 95% CI = 0.70-1.22), dominant model (OR = 0.99, 95% CI = 0.76-1.28) or recessive model (OR = 1.07, 95% CI = 0.83-1.37). The meta-analysis suggests that there is no evidence for the association between ACE gene I/D polymorphism and PD risk.

LEP gene variant is associated with prostate cancer but not with colorectal cancer

The leptin (LEP) gene has been considered to be implicated in the development of cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of LEP rs7799039 variant with colorectal and prostate cancer risk. Published literatures from PubMed and Embase were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (2,596 colorectal cancer cases and 3,240 controls) for association of LEP rs7799039 variant with colorectal cancer, and three studies (1,343 prostate cancer cases and 1,238 controls) for association with prostate cancer were included in the meta-analysis. For colorectal cancer, there was no significant association of LEP rs7799039 variant with this disease under homogeneous co-dominant model (OR = 0.88, 95 % CI = 0.75-1.02), heterogeneous co-dominant model (OR = 1.00, 95 % CI = 0.89-1.13) and dominant model (OR = 0.97, 95 % CI = 0.87-1.08); however, there was a marginal association under recessive model (OR = 0.87, 95 % CI = 0.76-0.99). For prostate cancer, there was significant association of LEP rs7799039 variant with this disease under homogeneous co-dominant model (OR = 1.33, 95 % CI = 1.06-1.67) and recessive model (OR = 1.26, 95 % CI = 1.05-1.51), but not under heterogeneous co-dominant model (OR = 1.24, 95 % CI = 0.87-1.77) and dominant model (OR = 1.30, 95 % CI = 1.84). The present meta-analysis demonstrated that the LEP rs7799039 variant was associated with prostate cancer, but not with colorectal cancer.

The CYP11B2 −344C/T variant is associated with ischemic stroke risk: An updated meta-analysis

The CYP11B2 gene has been suggested to play an important role in the pathogenesis of ischemic stroke. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of the CYP11B2 -344C/T variant with ischemic stroke. Published literature from PubMed and Embase were retrieved. Pooled odds ratio with 95% confidence interval was calculated using a fixed- or random-effects model. A total of seven studies (2765 stroke cases and 3118 controls) for the CYP11B2 -344C/T variant were included in the meta-analysis. The meta-analysis indicated that the CYP11B2 -344C/T variant was significantly associated with ischemic stroke under a homogeneous co-dominant model (TT vs. CC: odds ratio=2.04, 95% confidence interval=1.21-3.45), dominant model (TT+TC vs. CC: odds ratio=1.67, 95% confidence interval=1.09-2.57) and recessive model (TT vs. TC+CC: odds ratio=1.56, 95% confidence interval=1.18-2.05) but not under a heterogeneous co-dominant model (TC vs. CC: odds ratio=1.43, 95% confidence interval=0.98-2.07). Further subgroup analysis showed that the CYP11B2 -344C/T variant was significantly associated with ischemic stroke in East Asian and South Asian populations, but not in a Caucasian population. The present meta-analysis supported the positive association of the CYP11B2 -344C/T variant with ischemic stroke. Further large-scale studies considering gene-gene/gene-environment interactions should be conducted to investigate the association.

TGF-β1 −509C/T (or +869T/C) polymorphism might be not associated with hepatocellular carcinoma risk

Many studies have reported the role of transforming growth factor-β1 (TGF-β1) -509C/T or +869T/C polymorphism with hepatocellular carcinoma (HCC) risk. However, these studies have yielded conflicting results. Hence, we performed this meta-analysis to investigate the association between TGF-β1 -509C/T or +869T/C polymorphism and HCC. A total of 11 studies including 2,577 HCC cases and 4,107 controls were included in the meta-analysis. Overall, TGF-β1 -509C/T (or +869T/C) polymorphism was not associated with HCC risk (homogeneous co-dominant model: OR = 1.29, 95 % CI = 0.88-1.89; heterogeneous co-dominant model: OR = 1.15, 95 % CI = 0.91-1.45; dominant model: OR = 1.14, 95 % CI = 0.87-1.48; recessive model: OR = 1.15, 95 % CI = 0.89-1.49). In the subgroup analysis, TGF-β1 -509C/T (or +869T/C) polymorphism was significantly associated with HCC risk in Caucasians under the recessive model (OR = 1.65, 95 % CI = 1.07-2.55) but not in other genetic models. In addition, we did not observe significant association in Asians under all genetic models. In conclusion, our meta-analysis indicates that TGF-β1 -509C/T (or +869T/C) polymorphism was not associated with risk of HCC, although a marginal association was found for Caucasians. However, a study with the larger sample size is needed to further evaluate gene-environment interaction on the association.

CYP17A1 T-34C polymorphism is not associated with endometrial cancer risk

The association between CYP17A1 T-34C polymorphism and endometrial cancer risk has been inconsistent and underpowered. To clarify the effect of CYP17A1 T-34C polymorphism on the risk of endometrial cancer, a meta-analysis of all available studies relating CYP17A1 T-34C polymorphism to the risk of endometrial cancer was conducted. The authors searched PubMed, EMBASE, Scopus, and VisionCite databases updated on March 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated. Finally, seven studies with 1,570 endometrial cancer cases and 2,474 controls were included in the meta-analysis. There was no statistically significant association between CYP17A1 T-34C polymorphism and endometrial cancer under heterogeneous codominant model (OR = 0.91, 95 %CI = 0.68-1.21). Although CYP17A1 T-34C polymorphism was marginally associated with endometrial cancer risk under homogeneous codominant model (OR = 0.69, 95 %CI = 0.49-0.99), the significant association was not stable after sensitivity analysis. We concluded that CYP17A1 T-34C polymorphism might not be one risk factor in the carcinogenesis of endometrial cancer. Further large and well-designed studies are needed to confirm this association.

XRCC3 T241M polymorphism is associated risk of hepatocellular carcinoma in the Chinese

The X-ray repair cross-complementing group 3 (XRCC3) gene has been suggested to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of XRCC3 Thr241Met variant with HCC. The published literature from PubMed, Chinese National Knowledge Infrastructure, and Wan Fang data was retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (1,531 HCC cancer cases and 1,952 controls) for XRCC3 Thr241Met variant were included in the meta-analysis. The meta-analysis showed that XRCC3 Thr241Met variant was associated with HCC risk under homogeneous codominant model (OR = 3.99, 95 % CI = 1.74-9.13) and recessive model (OR = 5.22, 95 % CI = 3.65-7.48), but not under heterogeneous codominant model (OR = 1.18, 95 % CI = 0.68-2.05) and dominant model (OR = 1.37, 95 % CI = 0.73-2.57). Subgroup analysis by ethnicity suggested that XRCC3 Thr241Met variant was associated with HCC risk in Chinese population, but not in Pakistani population. The present meta-analysis supported the positive association of XRCC3 Thr241Met variant with HCC in the Chinese. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

Polymorphisms of excision repair gene XPD Lys751Gln and hOGG1 Ser326Cys might not be associated with hepatocellular carcinoma risk: a meta-analysis

The xeroderma pigmentosum group D (XPD) and human 8-oxoguanine glycosylase 1 (hOGG1) genes have been suggested to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations of polymorphisms of XPD and hOGG1 genes with HCC risk. Published literature from PubMed, EMBASE, and Chinese National Knowledge Infrastructure were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using a fixed- or random-effects model. Seven studies (1,955 HCC cases and 2,023 controls) for XPD Lys751Gln polymorphism and six studies (1,470 HCC cases and 1,541 controls) for hOGG1 Ser326Cys polymorphism were included in the final meta-analysis. For XPD Lys751Gln polymorphism, no significant association was found under all genetic models (Gln/Gln vs Lys/Lys OR = 1.09, 95 % CI = 0.28-4.18; Gln/Lys vs Lys/Lys OR = 1.41, 95 % CI = 0.81-2.44; dominant model OR = 1.40, 95 % CI = 0.77-2.57; recessive model OR = 1.02, 95 % CI = 0.33-3.23). For hOGG1 Ser326Cys polymorphism, there was a significant association of this polymorphism with HCC risk under heterogeneous codominant model (OR = 1.38, 95 % CI = 1.01-1.88) and dominant model (OR = 1.57, 95 % CI = 1.14-2.16). The sensitivity analysis indicated that the significant association between hOGG1 Ser326Cys polymorphism and HCC risk was not robust. The present meta-analysis has limited evidence to support the association of XPD Lys751Gln and hOGG1 Ser326Cys polymorphisms with HCC risk. Further, large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

The −344C/T polymorphism in the CYP11B2 gene is associated with essential hypertension in the Chinese

It has been suggested that the -344C/T polymorphism in the CYP11B2 gene is involved in the development of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the association of -344C/T polymorphism in the CYP11B2 gene with hypertension risk in the Chinese population. Published literature from PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang data were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a fixed or random effects model. A total of 29 studies (8482 cases/8560 controls) were included in the final meta-analysis. Overall, there was a significant association between -344T/C polymorphism in the CYP11B2 gene and hypertension in the Chinese (heterogeneous co-dominant model: OR=1.10, 95% CI=1.03-1.17, I (2)=12.7%, p for heterogeneity=0.271; dominant model: OR=1.11, 95% CI=1.02-1.20, I (2)=32.1%, p for heterogeneity=0.051; allelic model: OR=1.08, 95% CI 1.01-1.16, p for heterogeneity=0.006). In the stratified analysis, the effect size was significant only in the Han Chinese (heterogeneous co-dominant model: OR=1.11, 95% CI=1.03-1.20, I (2)=0.0%, p for heterogeneity=0.745; dominant model: OR=1.11, 95% CI=1.02-1.21, I (2)=18.1%, p for heterogeneity=0.299; allelic model: OR=1.09, 95% CI 1.00-1.18, p=0.028), but not in the minority Chinese. Our study suggested that the -344T/C polymorphism in the CYP11B2 gene was significantly associated with hypertension in the Chinese population, especially in the Han Chinese.

Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.

Genetic polymorphisms of ALDH2 and ADH2 are not associated with risk of hepatocellular carcinoma among East Asians

The aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 2 (ADH2) genes have been implicated in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between polymorphisms of ALDH2 and ADH2 genes and HCC. Published literatures from PubMed and Embase were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Ten studies including 1,231 HCC cases and 1,849 controls were included in the meta-analysis of the association between ALDH2 polymorphism and HCC risk. The results indicated that ALDH2 polymorphism was not significantly associated with risk of HCC (homogeneous co-dominant model: OR = 0.99, 95% CI 0.72-1.34; heterogeneous co-dominant model: OR = 0.90, 95% CI 0.75-1.08; dominant model: OR = 0.91, 95% CI 0.70-1.18; recessive model: OR = 1.11, 95% CI 0.66-1.87). In addition, four studies including 518 cases and 607 controls were included in the meta-analysis of the association between ADH2 polymorphism and HCC risk. There was no association between ADH2 polymorphism and HCC risk (homogeneous co-dominant model: OR = 0.93, 95% CI 0.58-1.51; heterogeneous co-dominant model: OR = 1.39, 95% CI 0.87-2.23; dominant model: OR = 1.19, 95% CI 0.76-1.88; recessive model: OR = 0.91, 95% CI 0.54-1.54). Further analysis suggested that the ALDH2 polymorphism-alcohol interaction was marginally associated with HCC risk under the dominant model (OR = 2.05, 95% CI 1.01-4.17). However, the result was not robust by sensitivity analysis. The results from the present meta-analysis indicated that there was no significant association between ALDH2 polymorphism, ADH2 polymorphism, or ALDH2 polymorphism-alcohol intake interaction and HCC risk in the East Asians.