Genetic polymorphisms in MMP 2, 3 and 9 genes and the susceptibility of osteosarcoma in a Chinese Han population

Background: There are no data about the role of MMPs polymorphism in development of osteosarcoma.

Patients and methods: Two-hundred fifty-one patients with osteosarcoma and 251 healthy controls were included to investigate the association between the MMP2, 3, 9 polymorphisms and the risk of osteosarcoma.

Results: Compared with the MMP2 SNP rs243865 homozygote CC, The heterozygous CT genotype was associated with significantly increased risk for osteosarcoma (OR?=?1.86, 95% CI?=?1.18–4.22, p?=?0.014); the TT genotype was associated with increased risk for osteosarcoma (OR?=?1.92, 95% CI?=?1.21–3.52, p?=?0.028). However, the genotype and allele frequencies of MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were not significantly different.

Conclusion: MMP2 rs243865 genotype was associated with increased risk for development of osteosarcoma in Chinese Han population.     

Association between polymorphisms in AXIN1 gene and atrial septal defect

Abstract

Context: AXIN1 is a central component of Wnt signalling pathway which is essential for embryonic development.

Objective: To investigate whether polymorphisms of AXIN1 contribute to ASD susceptibility.

Materials and methods: Three tag SNPs (rs12921862, rs370681 and rs1805105) in AXIN1 were genotyped in 208 ASD patients and 302 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a Chinese population.

Results: Significantly increased ASD risk was observed to be associated with the A allele of rs12921862 (p?<?0.0001, OR?=?3.096, 95% CI?=?2.037–4.717). Increased ASD risk was observed to be associated with rs370681 in a codominant (p?=?0.043, OR?=?1.52, 95% CI?=?1.04–2.22) and overdominant model (p?=?0.016, OR?=?1.57, 95% CI?=?1.08–2.27).

Conclusion: rs12921862 and rs370681 may contribute to ASD susceptibility.     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR?=?1.12, 95% CI: 0.88–1.44, p?=?0.36; BB genotype: OR?=?1.15, 95% CI: 0.81–1.62, p?=?0.43; bb genotype: OR?=?0.86, 95% CI: 0.61–1.20, p?=?0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.     

Long non-coding RNA POLR2E gene polymorphisms increased the risk of prostate cancer in a sample of the Iranian population

The current study aimed to examine the impact of POLR2E rs1046040 and rs3787016 polymorphisms on prostate cancer (PCa) risk in a sample of southeast Iranian population. The present case-control study was performed on 178 patients with PCa and 180 benign prostatic hyperplasia (BPH). Genotyping of the variants was done by mismatch PCR-RFLP. The findings showed that the rs3787016 C?>?T variant significantly increased the risk of PCa in codominant (OR?=?1.84, 95% CI?=?1.12-3.03, P?=?0.018, CT vs CC), dominant (OR?=?1.88, 95% CI?=?1.63-3.05, P?=?0.011, CT?+?TT vas CC) and allele (OR?=?1.77, 95% CI?=?1.52-2.72, P?=?0.010, T vs C) inheritance model. Regarding rs1046040 C?>?T polymorphism, the findings revealed that the CT genotype significantly increased the risk of PCa compared to the CC genotype (OR?=?1.60, 95% CI?=?1.03-2.49, P?=?0.043). Furthermore, rs3787016 CT/rs1046040?CC as well as rs3787016 CT/rs1046040 CT increased the risk of PCa compared to the CC/CC genotype (p?=?0.029 and p?=?0.014, respectively). Haplotype analysis proposed that rs3787016 T/rs1046040 C significantly increased the risk of PCa compared to C/C (p?=?0.037). No significant association was observed between POLR2E variants and clinicopathological characteristics of PCa patients. In conclusion, the findings propose that POLR2E variants may be a risk factor for susceptibility to PCa in a sample of Iranian population.     

A LncRNA gene polymorphism (rs1814343) is associated with the risk of coronary artery lesions in southern Chinese Kawasaki disease patients

Background

Kawasaki disease (KD) is a multisystemic angiitis, and its most disastrous complication is coronary artery lesions (CALs). Recently, the role of long non-coding RNAs (lncRNAs) in KD has been reported. rs1814343 is a lncRNA, but the relationship between the lncRNA rs1814343 polymorphism and KD risk remains elusive.

Methods

We enrolled 1625 Kawasaki disease patients (583 patients with CAL and 1042 without CAL) and 1000 healthy controls from a southern Chinese population. We genotyped the rs1814343 C > T polymorphism in KD and control patients using the TaqMan method. The odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association.

Results

There was no significant association between the lncRNA rs1814343 C > T polymorphism and KD susceptibility. However, we stratified patients in this study by CAL and sex. First, compared with the control groups, we found that the rs1814343 genotype increased risk for KD patients with CAL (TT vs. CC + CT: OR = 1.36, 95% CI = 1.08–1.71, p = 0.009). Moreover, when KD patients were stratified by CAL, the TT genotypes of this lncRNA polymorphism contributed to a relatively higher occurrence of KD with CAL than that was found in the CC/CT genotype patients (TT vs. CC + CT: OR = 1.35, 95% CI = 1.07–1.69, p = 0.011). In addition, our research suggested that the TT variant genotype in the lncRNA rs1814343 had an obvious risk of KD with CAL susceptibility in male children.

Conclusion

The lncRNA rs1814343 C > T polymorphism was related to higher susceptibility of KD with CAL.     

Interleukin 17A rs3819024 A>G polymorphism is associated with an increased risk of gastric cardia adenocarcinoma in a Chinese population

Abstract

Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors. In addition to environmental risk factors, genetic factors might play an important role in GCA carcinogenesis. To evaluate the association between polymorphisms in the interleukin 17A (IL17A) gene on the development of GCA, we conducted a hospital-based case–control study. A total of 243 GCA cases and 476 controls were recruited and their genotypes were determined using a custom-by-design 48-Plex SNPscan? Kit. IL17A rs3819024 A?>?G polymorphism was found to be associated with the increased risk of GCA. When the IL17A rs3819024 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly increased risk of GCA (AG versus AA: adjusted OR?=?1.53, 95% CI?=?1.05–2.23, p?=?0.026). However, there was no significant association between five other SNPs and GCA. Stratified analyses indicated that a significantly increased risk of GCA associated with the IL17A rs3819024 A?>?G polymorphism was evident among male patients, patients who drank alcohol or those who never smoked. These findings indicated that functional polymorphism IL17A rs3819024 A?>?G might contribute to GCA susceptibility. Future larger studies with more rigorous study designs are required to confirm the current findings.     

The first evidence of an association between a polymorphism in the endocannabinoid-degrading enzyme FAAH (FAAH rs2295633) with attention deficit hyperactivity disorder

Several single nucleotide polymorphisms (SNPs) of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the endocannabinoids, have been shown to be associated with many neuropsychiatric disorders. Here, FAAH rs2295633 was studied in ADHD and case-control healthy children. There was a significant difference in the allele frequency (P = .04) and genotype distribution (P = .04) of the FAAH rs2295633 between ADHD cases and controls. The ADHD children appeared to have less of TT genotype (OR 0.396, 95% CI 0.178–0.884, p = .024) and T allele (OR 0.658, 95% CI 0.440–0.982, p = .04). To our best knowledge, this is the first statistical significant association between FAAH rs2295633 genotype and ADHD disorder. Larger sample sizes and functional studies are warranted to explore the clinical utility of FAAH genotyping as a possible marker for increased ADHD risk in children.     

Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population

Background: Common single‐nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre‐miRNAs (miR‐196a2, miR‐146a, and miR‐499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori‐induced gastritis in Japanese population. Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non‐cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non‐ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases. Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non‐cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02–1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non‐cancer and non‐ulcer subjects (OR = 1.39, 95%CI = 1.00–1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09–2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non‐cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0–1 vs 2～, adjusted OR = 1.62, 95%CI = 1.05–2.49, p =.03). Conclusions: The rs2910164 (G>C) SNP in the miR‐146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR‐196a2 is associated with the degree of H. pylori‐induced mononuclear cell infiltration.     

Interactive effects of CDKN2B-AS1 gene polymorphism and habitual risk factors on oral cancer

Oral squamous cell carcinoma (OSCC) is a common malignant disease associated with a high mortality rate and heterogeneous disease aetiology. Cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), is a long noncoding RNA that has been shown to act as a scaffold, sponge, or signal hub to promote carcinogenesis. Here, we attempted to assess the effect of CDKN2B-AS1 single-nucleotide polymorphisms (SNPs) on the susceptibility to OSCC. Five CDKN2B-AS1 SNPs, including rs564398, rs1333048, rs1537373, rs2151280 and rs8181047, were analysed in 1060 OSCC cases and 1183 cancer-free controls. No significant association of these five SNPs with the risk of developing OSCC was detected between the case and control group. However, while examining the clinical characteristics, patients bearing at least one minor allele of rs1333048 (CA and CC) were more inclined to develop late-stage (stage III/IV, adjusted OR, 1.480; 95% CI, 1.129–1.940; p = 0.005) and large-size (greater than 2 cm in the greatest dimension, adjusted OR, 1.347; 95% CI, 1.028–1.765; p = 0.031) tumours, as compared with those homologous for the major allele (AA). Further stratification analyses demonstrated that this genetic correlation with the advanced stage of disease was observed only in habitual betel quid chewers (adjusted OR, 1.480; 95% CI, 1.076–2.035; p = 0.016) or cigarette smokers (adjusted OR, 1.531; 95% CI, 1.136–2.063; p = 0.005) but not in patients who were not exposed to these major habitual risks. These data reveal an interactive effect of CDKN2B-AS1 rs1333048 with habitual exposure to behavioural risks on the progression of oral cancer.     

The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p?<?0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p?=?0.04) and rs2294021 CT genotype (p?=?0.01) in female patients compared to controls. ACC (p?=?0.04) and ATC haplotypes (p?=?0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p?<?0.0001), shorter EFS, increased death rate (p?=?0.002) and shorter OS compared to C genotype (p?=?0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p?=?0.02) and those with rs2294021 CT had longer EFS and OS (p?<?0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.

     

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease

Abstract

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease (ESRD) from the published reports is still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the iPTH level among patients with ESRD. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with iPTH level among patients with ESRD. In this meta-analysis, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations (Bb versus bb: OR?=?61.40, 95% CI: 19.65–103.16, p?=?0.004). However, the iPTH level in ESRD patients carrying BB genotype was not significant different from that in ESRD patients with Bb genotype and bb genotype in overall populations (BB versus Bb: OR?=??18.30, 95% CI: ?126.28–89.69, p?=?0.74; BB versus bb: OR?=?22.85, 95% CI: ?70.81–116.51, p?=?0.63). Furthermore, the results for Caucasians were similar to those in overall populations. In conclusion, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations and in Caucasians. However, more studies should be conducted to confirm it.     

A systematic review and meta-analysis of the association of transforming growth factor β receptor I 6A/9A gene polymorphism with ovarian cancer risk

Abstract

Ovarian cancer is the leading cause of cancer-related death in women. This meta-analysis was conducted to evaluate the association of transforming growth factor β receptor I (TβR-I) 6A/9A gene polymorphism with ovarian cancer risk. The association literatures were identified from PubMed and Cochrane Library on 1 October 2013, and eligible reports were recruited and synthesized. Four reports were recruited into this meta-analysis for the association of TβR-I 6A/9A gene polymorphism with ovarian cancer risk. 6A allele and 6A/6A genotype of TβR-I were associated with the ovarian cancer risk (6A: OR?=?1.24, 95% CI: 1.02–1.51, p?=?0.03; 6A/6A: OR?=?2.30, 95% CI: 1.01–5.22, p?=?0.05). However, TβR-I 9A/9A genotype was not associated with the risk of ovarian cancer (OR?=?0.82, 95% CI: 0.66–1.02, p?=?0.08). In conclusion, TβR-I 6A allele and 6A/6A genotype are associated with the ovarian cancer risk. However, more studies should be performed to confirm this relationship in the future.     

A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case–control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05–1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03–1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m², adjusted OR = 1.34, 95% CI = 1.12–1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m², adjusted OR = 1.0², 95% CI = 0.86–1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.     

Association of rs2954029 and rs6982502 Variants with Coronary Artery Disease by HRM Technique: A GWAS Replication Study in an Iranian Population

Background:Genome-wide association studies (GWAS) have been the primary tool for an unbiased study of the genetic background of coronary artery disease (CAD). They have identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). In this study, we aimed to replicate the association of rs2954029 and rs6982502, a GWAS identified SNP, to CAD in an Iranian population.Methods:A sample of 285 subjects undergoing coronary angiography, including 134 CAD patients and 151 healthy. The genotype determination of rs2954029 and rs6982502 SNPs performed using the high-resolution melting analysis (HRM) technique.Results:Our results revealed that the TT genotype of rs2954029 (p= 0.009) and rs6982502 (p< 0.001) were significantly higher in CAD patients compared with controls. Binary logistic regression showed that rs6982502 and rs2954029 increase the risk of CAD incidence (2.470 times, p= 0.011, 95% CI= [1.219-4.751], and 2.174 times, p= 0.033, 95% CI= [1.066-4.433] respectively). After adjusting for confounders, we found that rs6982502 and rs2954029 are significantly associated with CAD risk.Conclusion:These data showed that the TT genotype of rs2954029 and rs6982502 is associated with the risk of CAD in a hospital-based sample of the Iranian population, which has replicated the result of recent GWAS studies.Key Words: Coronary Artery Disease (CAD), Genome-Wide Association Studies (GWAS), High-Resolution Melting (HRM), Single-Nucleotide Polymorphisms (SNP)     

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.     

The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population

BACKGROUND: Nonsyndromic cleft lip and/or cleft palate (NSCLP) are common congenital anomalies in humans, the etiologies of which are complex and associated with both genetic and environmental factors. Previous data suggested single nucleotide polymorphisms (SNPs) of rs1546124, rs4783099, and rs16974880 of the CRISPLD2 gene were associated with an increased risk of NSCLP; however, subsequent studies have yielded conflicting results. This study aims to evaluate the associations of the aforementioned polymorphisms with NSCLP in a Northwestern Chinese population. METHODS: Three CRISPLD2 SNPs were genotyped in a case‐control study (n = 907), including 444 NSCLP patients and 463 healthy individuals, using polymerase chain reaction–denaturing high‐performance liquid chromatography (PCR‐DHPLC). RESULTS: The genotype and allele frequencies of rs1546124 (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.58–3.34; p = 1 × 10⁻⁵) and rs4783099 (OR, 0.73; 95% CI, 0.54–1.00; p = 0.05) were different in NSCLP patients compared with controls. Furthermore, the CC genotype at rs1546124 was associated with increased risk for cleft lip with or without cleft palate (CL/P; OR, 2.11; 95% CI, 1.41–3.15; p_correct = 1.5 × 10⁻⁴) and for cleft palate only (CPO; OR, 2.93; 95% CI, 1.69–5.07; p_correct = 5.4 × 10⁻⁴), whereas the T allele of rs4783099 was associated with decreased risk for CPO. Further gender stratification showed that the statistical association of these two loci is mainly in the male patients, and not in female patients. CONCLUSION: Our results suggest that the CRISPLD2 gene contributes to the etiology of NSCLP in the Northwestern Chinese population. SNP rs1546124 is significantly related to NSCLP, associated with both CL/P and CPO groups, and SNP rs4783099 is significantly associated with CPO. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk

Abstract

Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) ?2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR?=?1.19; 95% CI: 0.97–1.45; p?=?0.10; AA genotype: OR?=?1.27; 95% CI: 0.95–1.70; p?=?0.11; GG genotype: OR?=?0.77; 95% CI: 0.57–1.05; p?=?0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR?=?1.45; 95% CI: 1.05–2.00; p?=?0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.     

Potential impact of ADAM-10 genetic variants with the clinical features of oral squamous cell carcinoma

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM-10) involves in the tumour progression, but the impacts of single-nucleotide polymorphism (SNP) of ADAM-10 on oral squamous cell carcinoma (OSCC) remain unclear. The aim of this study was to investigate the influence of SNP of ADAM-10 on the clinical features of OSCC in male Taiwanese. Five loci of ADAM-10 SNPs including rs653765 (C/T), rs2305421 (A/G), rs514049 (A/C), rs383902 (T/C) and rs2054096 (A/T) were genotyped by TaqMan allelic discrimination in 1138 OSCC patients and 1199 non-OSCC individuals. The ADAM-10 SNP rs2305421 GG (AOR: 1.399, 95% CI: 1.045–1.874, p = 0.024) and G allele (AOR: 1.170, 95% CI: 1.012–1.351, p = 0.034) illustrated a significantly higher genotypic frequencies in the OSCC group compared to the distribution of the ADAM-10 SNP rs2305421 AA wild type. In the subgroup analysis, the ADAM-10 SNP rs383902 TC+CC was significantly correlated to tumour size larger than T2 in betel quid chewer (AOR: 1.375, 95% CI: 1.010–1.872, p = 0.043), while the ADAM-10 SNP rs653765 CT+TT was significantly associated with tumour size larger than T2 in cigarette smoker (AOR: 1.346, 95% CI: 1.023–1.772, p = 0.034). The results from The Cancer Genome Atlas revealed highest ADAM-10 mRNA level in T2 stage of current smokers with head and neck squamous cell carcinoma (HNSCC). In conclusions, the ADAM-10 SNP rs2305421 G allele is associated with the presence of OSCC, and the ADAM-10 SNP rs383902 TC+CC and ADAM-10 SNP rs653765 CT+TT correlates to large tumour size in specific conditions.