Association Between rs1344706 of ZNF804A and Schizophrenia:A Meta-analysis

Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of Pub Med database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis,involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio（OR） with 95% confidence interval（CI） was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations（P = 0.028, OR = 1.138, 95% CI：1.014–1.278; P = 0.004 for heterogeneity） and Asian populations（P = 0.008, OR = 1.092, 95%CI： 1.023–1.165; P = 0.001 for heterogeneity）, but not in other populations（P = 0.286,OR = 1.209, 95% CI： 0.853–1.714, P = 0.120 for heterogeneity）. Egger’s test（P 〉 0.05） and Begg’s test（P 〉 0.05） are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.     

An Exploratory Study of the Association between KCNB1 rs1051295 and Type 2 Diabetes and Its Related Traits in Chinese Han Population

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.     

The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA''s properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.     

Association of C-reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer

The correlation between rs1205, rs2808630 variants of C-reactive protein (CRP) gene and susceptibility of cancer has been assessed previously, but with conflicting results. We adopted odds ratios (ORs) with 95% confidence intervals (CIs), in silico tools and enzyme-linked immunosorbent assay (ELISA) analysis to evaluate this association. Totally, 10,614 cancer subjects and 33,294 controls were involved in the pooled analysis. When all the studies were pooled, no significant correlation was indicated between the two variants and cancer risk. However, in stratification analysis by ethnicity, we found that CRP rs1205 C>T polymorphism was associated with an elevated risk of cancer in Asians (T-allele vs. C-allele, OR = 1.20, 95% CI = 1.06–1.36, p_{heterogeneity} = .226; TT vs. CC, OR = 1.48, 95% CI = 1.14–1.93, p_{heterogeneity} = .089). Similar findings were observed for rs2808630 variant. In silico tools showed that lung adenocarcinoma participants with high CRP expression may have shorter overall survival time than low expression group. ELISA analysis indicated that CRP expression in prostate adenocarcinoma subjects with TT + TC genotypes was statistically higher than in those with CC genotypes. CRP rs1205 C>T and rs2808630 T>C polymorphism may be associated with cancer risk, especially for Asians.     

Association study of rs10768683 and rs968857 polymorphisms with transfusion-dependent thalassemia (TDT) in a southern Iranian population

Previous studies reported that detection of polymorphisms inherited through paternal model could be potential markers for the Non-Invasive Prenatal Diagnosis (NIPD) of β-thalassemia. The aim of the current study was to find out the associations of rs10768683 and rs968857 with transfusion-dependent thalassemia (TDT) in a southern Iranian population. A total of 175 subjects were investigated, divided into patients with TDT as case group (n?=?75) and healthy people as control group (n?=?100). Genomic DNAs were extracted from peripheral blood using salting out procedure. Genotyping rs10768683 and rs968857 was carried out by ARMS-PCR, then statistical analyses were assessed using SPSS, and Medcalc ver. 18 software. Data showed that rs10768683 was statistically significant in co-dominant model of inheritance (P?=?0.025, OR?=?2.11 [1.08-4.15]) and genotype frequencies of CG among controls and cases were 0.68 and 0.80, respectively. However, according to genotype frequencies, there was no association between rs968857 and TDT among cases and healthy controls in any models of inheritance. In conclusion, the present study showed the association of rs10768683 with major β-thalassemia through ARMS-PCR technique.     

Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P  = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P  = 5.47^e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P  = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P  = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P  = 0.0046) and CG genotypes (OR = 2.2249; P  = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P  = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant.     

Association of the LINGO2-related SNP rs10968576 with body mass in a cohort of elderly Swedes

Genome-wide association studies (GWAS) have identified common genetic factors influencing body mass as well as body adiposity. The functional implications of these loci are currently under investigation. Intense scrutiny of the body mass-associated FTO locus revealed age-specific effects, or a weakened effect in elderly populations. In this study, we aimed to determine the effects of single nucleotide polymorphisms (SNPs) representing 35 GWAS-identified body mass- and adiposity-associated genetic loci. In our analysis, 949 participants of the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were included. All participants were born between 1920 and 1924. Data were available for 474 male and 475 female participants at age 70 and 380 male and 390 female participants at age 75. Genetic associations with BMI and change in BMI from age 70 to 75 were analyzed. In our analysis, rs10968576, an intronic SNP within the LINGO2 (LERN3, LRRN6C) gene, was associated with body mass in a cross section of elderly Swedes at age 70. This is the first study to replicate the association of a LINGO2-related genetic variant with body mass in an independent cohort of elderly citizens.     

Association of resistin (rs3745367) and urotensin II (rs228648 and rs2890565) gene polymorphisms with risk of type 2 diabetes mellitus in Indian population

Molecular Biology Reports - Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the...     

Association between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohort

The MYH9 gene encodes a protein that is expressed in the kidney glomerular podocytes. MYH9 single nucleotide polymorphisms (SNPs) have been linked to the risk for chronic kidney disease (CKD) and end stage renal disease. Our aim was to determine whether MYH9 SNPs were associated with renal disease in Spanish Caucasians. The RENASTUR cohort consisted of 592 Spanish Caucasians, aged 55–85 years. They were genotyped for SNPs rs3752462 and rs4821480, which tagged haplotype E. The main values between individuals with a glomerular filtration rate (eGFR) < 60 and ≥ 60 ml/min/1.73 m² were statistically compared. The next variables were significantly associated with the eGFR in the univariate analysis: age, gender, type 2 diabetes, total cholesterol, total LDL-cholesterol, and the MYH9 rs3752462 (TC + TT genotypes; p = 0.003). This SNP remained significantly associated with the eGFR in the multivariate analysis.     

Association between vitamin D receptor (FokI) genetic variant rs2228570 and iron profile in hemodialysis patients

Iron deficiency is a common etiology of anemia that causes suboptimal response to erythropoietin therapy in hemodialysis (HD) patients. This study investigated the association between vitamin D receptor (VDR) genetic variant (FokI) rs2228570 with iron indices (serum iron, transferrin, transferrin saturation, and ferritin). Sixty adequately hemodialyzed patients subdivided into two groups; 31 patients with transferrin saturation (TSAT)?<?20% and 29 with TSAT?>?20% who received I.V sodium ferric gluconate, calcium, and vitamin D. Sixty normal healthy were selected as the control group.. VDR genetic variant (SNP rs2228570) was genotyped in all subjects using PCR/RFLP. HD patients showed a higher frequency of rs2228570 FF genotype (38.3%) than controls (31.7%). The frequency of ff genotype and f allele in patients (8.4 and 35% respectively) were significantly lower than controls (25 and 46.7% respectively). Allele model (f vs. F): OR 0.721, 95% CI 0.521–0.998, P?=?0.049. While (ff vs. FF): OR 0.452, 95% CI 0.223–0.917, P = 0.028. The distribution of Ff?+?ff genotypes in HD cases with TSAT?>?20% was higher than in HD cases with TSAT?<?20%, Dominant model (Ff +ff vs FF): OR 2.753, 95% CI 1.902–3.409, P?=?0.048. f allele showed lower frequency in low TSAT group than high TSAT group (27.4 vs. 43.1%) with significant P value (P?=?0.042) with allele model (f vs. F): OR 2.012, 95% CI 1.923–4.226, P?=?0.042. Fok-1 ff, Ff?+?ff genotypes were significantly associated with TSAT?>?20% with a protective effect against low TSAT in HD patients.

     

Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese

The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population.     

Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity

In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.     

Lack of association between SNP rs3914132 of the RELN gene and otosclerosis in India

Otosclerosis (MIM 166800) is primarily a metabolic bone disorder of the otic capsule, which leads to bony fixation of the stapedial footplate in the oval window; it is among the most common causes of acquired hearing loss. The etiology of this disease is largely unknown, although epidemiological studies suggest the involvement of both genetic and environmental factors. Recently, a reelin gene, SNP rs3914132, located in intron 2, was shown to be associated with otosclerosis in a European population. When we sequenced blood DNA samples of 85 individuals with otosclerosis and 85 controls, four SNPs of this gene: rs3914131 (P = 0.6463), rs3914132 (P = 0.1822), rs9641319 (P = 0.7371), and rs10227303 (P = 0.5669) were not significantly associated with this disease. In one familial case, a novel variant (C/T) at contig position 2923488 was found to be inherited by the proband and affected family members.     

Association between SNP rs527616 in lncRNA AQP4-AS1 and susceptibility to breast cancer in a southern Brazilian population

Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.     

Association between rs4673 (C/T) and rs13306294 (A/G) haplotypes of NAD(P)H oxidase p22phox gene and severity of stenosis in coronary arteries

Phagocytic NADH/NADPH oxidase is an important enzyme producing reactive oxygen species within subendothelial space of vessels. Findings have shown that p22phox subunit is an essential element related to the enzyme activity. Since some p22phox polymorphisms are thought to have functional roles in the enzyme thus, we studied the association between rs4673 (C242T) and rs13306294 (A/G) haplotypes and the severity of stenosis in coronary arteries. One hundred eighty-two subjects undergoing coronary angiography were recruited on the base of study design. Patients (n=114) had at least a stenosed coronary artery (>50% stenosis) and subdivided into three subgroups; SVD (n=28), 2VD (n=31) and 3VD (n=55) while controls (n=68) had the normal coronary arteries (<5% stenosis). The direct haplotyping technique of SNPs was performed using ARMS-RFLP-PCR method. Furthermore, alphabet-based tools predicted the changes of secondary structure at the rs4673 position. All haplotypes being proposed theoretically were found in the study population. The distribution of two-allele haplotypes had no significant difference between patients and controls (P=0.1). Although the rs4673 allele frequency was not significant between the groups (P>0.5), chi square test and multinomial regression analysis showed an observed high risk for rs13306294 A allele among patients. The bioinformatics tools predicted that the p22phox secondary structure is not changed due to the substitution of Tyr→His at the rs4673 position. We concluded that the polymorphisms have no allele linkage on the chromosome. In addition, the rs13306294 A allele is a potential factor of stenosis of coronary arteries that increases susceptibility for the extent of disease.     

Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a chinese population

Objective

To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population.

Methods

A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini''s Score System and counts of diseased vessels.

Results

Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup).

Conclusions

Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.