Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy

The mechanism of environmental factors in Kashin–Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin–responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin–responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

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Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis

International Journal of Hypertension ◽

10.1155/2020/9185697 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Zhiqiang Zhao ◽

Chunmei Gong ◽

Yanfang Gao ◽

Xiaoli Liu ◽

Sai Wu ◽

...

Keyword(s):

Propensity Score ◽

Propensity Score Matching ◽

Additive Model ◽

Recessive Model ◽

Cardiovascular Development ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Cross Sectional ◽

Single Nucleotide ◽

Propensity Score Matching Analysis

Cardiovascular development critical genes are key determinants in cardiovascular diseases. We hypothesize that SNPs in these genes may play critical roles in the development of hypertension. Therefore, we enrolled 516 paired hypertension patients and controls in a total of 2,742 subjects in a cross-sectional population study by the propensity score matching (PSM) method. Twenty-one SNPs from 5 cardiovascular developmental related genes were detected by the improved multiplex ligase detection reaction (iMLDR) method. Conditioned logistic regression under three different genetic models, namely, additive model, dominant model, and recessive model, was performed. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations of SNPs with hypertension. We found that the distribution of genotypes at rs833061, rs3025010, and rs699947 within the VEGFA gene and the distribution of alleles at rs3025010 in hypertension subjects were different from those in controls. Both rs833061 and rs3025010 were associated with hypertension in crude models, but only rs3025010 remains associated with hypertension after adjusting with confounding factors in the additive model and the dominant model. We also found that hypertension subjects with C/T and C/C genotypes at rs3025010 had lower SBP and DBP levels. In addition, rs3025010 could interact with rs6784267 within the CCM3 gene in the association. In conclusion, our findings suggest that rs3025010 may play a role in the pathogenesis of hypertension, which may be a potential target for individualized prevention and treatment of hypertension.

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Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children

International Journal of Endocrinology ◽

10.1155/2017/6437542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Lijun Wu ◽

Liwang Gao ◽

Xiaoyuan Zhao ◽

Meixian Zhang ◽

Jianxin Wu ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Multiple Testing ◽

Association Studies ◽

Statistical Significance ◽

Additive Model ◽

Recessive Model ◽

Chinese Children ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P=0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

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Association of Adiponectin Gene Polymorphism With Birth Weight in Korean Neonates

Twin Research and Human Genetics ◽

10.1017/thg.2013.16 ◽

2013 ◽

Vol 16 (3) ◽

pp. 732-738 ◽

Cited By ~ 2

Author(s):

Kyoung Ae Kong ◽

Young Ju Suh ◽

Su Jin Cho ◽

Eun Ae Park ◽

Mi Hye Park ◽

...

Keyword(s):

Birth Weight ◽

Fetal Growth ◽

Additive Model ◽

Recessive Model ◽

Ponderal Index ◽

Nucleotide Polymorphisms ◽

Adiponectin Gene ◽

Single Nucleotide ◽

Term Neonates

Adiponectin has been associated with insulin resistance and type 2 diabetes mellitus and possibly fetal growth. Our aim was to assess the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and the birth sizes. We investigated four SNPs of ADIPOQ (rs182052, rs2241766, rs1501299, and rs266729) and birth height and weight in 237 healthy full-term neonates. The neonates with the rs182052 G allele had a greater birth weight (p = .043 in the dominant model) and a higher ponderal index (p = .028 in the additive model). The rs2241766 G allele was associated with a greater birth weight (p = .016 in the recessive model). In a logistic regression analysis, the homozygotes for the rs182052 G allele and those for the rs2241766 G allele showed a significant association with a greater birth weight above 90 percentile (OR 2.75, 95% CI 1.13–6.70 and OR 5.15, 95% CI 1.66–15.99, respectively). In conclusion, we found an association between rs182052 and rs2241766 and birth weight and ponderal index among healthy neonates and suggested that adiponectin might have some roles in fetal growth.

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Association between RBMS1 gene rs7593730 and BCAR1 gene rs7202877 and Type 2 Diabetes Mellitus in a Chinese Han Population

Acta Biochimica Polonica ◽

10.18388/abp.2017_1451 ◽

2018 ◽

Vol 65 (3) ◽

Cited By ~ 1

Author(s):

Elena Kazakova ◽

Meijun Chen ◽

Esma Jamaspishvili ◽

Zhang Lin ◽

Jingling Yu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Chinese Population ◽

Additive Model ◽

Recessive Model ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 had relationships with type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined the association of them with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP allele and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had a significant decreased T2DM risk compared to homozygous carriers of TT (p= 0.038, OR 0.44, 95 % CI 0.20-0.96). In the recessive model, the genotype GG carriers had a significant decreased T2DM risk compared to GT+TT (p= 0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of genotype CT and TT had significantly decreased T2DM risk compared with the carriers of genotype CC (CT: CC P=0.038, OR 0.71, 95%CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95%CI 0.13-0.76). In a dominant model, TT+CT: CC (p= 0.013, OR 0.673, 95 % CI 0.49-0.92) and in a recessive model, TT: CT+CC (p= 0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had a significant decreased T2DM risk compared to carriers of C (p= 0.002, OR 0.65, 95 % CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.

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Comprehensive assessment for miRNA polymorphisms in hepatocellular cancer risk: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20180712 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 5

Author(s):

Ben-Gang Wang ◽

Li-Yue Jiang ◽

Qian Xu

Keyword(s):

Systematic Review ◽

Hepatitis B Virus ◽

Odds Ratio ◽

Meta Analysis ◽

Hepatocellular Cancer ◽

Recessive Model ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

B Virus

MiRNA polymorphisms had potential to be biomarkers for hepatocellular cancer (HCC) susceptibility. Recently, miRNA single nucleotide polymorphisms (SNPs) were reported to be associated with HCC risk, but the results were inconsistent. We performed a systematic review with a meta-analysis for the association of miRNA SNPs with HCC risk. Thirty-seven studies were included with a total of 11821 HCC patients and 15359 controls in this meta-analysis. We found hsa-mir-146a rs2910164 was associated with a decreased HCC risk in the recessive model (P=0.017, OR = 0.90, 95% confidence interval (CI) = 0.83–0.98). While hsa-mir-34b/c rs4938723 was related with an increased HCC risk in the co-dominant model (P=0.016, odds ratio (OR) = 1.19, 95%CI = 1.03–1.37). When analyzing the Hepatitis B virus (HBV)-related HCC risk, hsa-mir-196a-2 rs11614913 was associated with a decreased HBV-related HCC risk in the co-dominant and allelic models. And hsa-mir-149 rs2292832 was found to be associated with a decreased HBV-related HCC risk in the dominant and recessive models. In conclusion, hsa-mir-146a rs2910164 and hsa-mir-34b/c rs4938723 could be biomarkers for the HCC risk while hsa-mir-196a-2 rs11614913 and hsa-mir-149 rs2292832 had potential to be biomarkers for HBV-related HCC risk.

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ASSOCIATION OF POLYMORPHISM RS6737848 IN THE SOCS5 GENE WITH BRONCHIAL ASTHMA

Annals of the Russian academy of medical sciences ◽

10.15690/vramn.v68i7.713 ◽

2013 ◽

Vol 68 (7) ◽

pp. 53-56

Author(s):

I. V. Saltykova ◽

M. B. Freidin ◽

E. Yu. Bragina ◽

L. M. Ogorodova ◽

V. P. Puzyrev

Keyword(s):

Immune Response ◽

Length Polymorphism ◽

Additive Model ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Restriction Fragments ◽

Asthma Patients ◽

Polymorphic Variants

Aim: to investigate the role of polymorphic variants of immune-response modifying genes in predisposition to asthma. Patients and methods. The analysis of restriction fragments length polymorphism was used to investigate 10 single-nucleotide polymorphisms: IFNG rs2069705, IFNGR2 rs17880053, IL4 rs 2070874, IL4RA rs 1805010, GATA3 rs10905277, TBX21 rs11652969, PIASY rs3760903, PIAS3 rs12756687, STAT5β rs16967593, and SOCS5 rs6737848 in 106 asthma patients and 115 healthy people. Results. The rs6737848 SOCS5 polymorphism was significantly associated with asthma in additive model (р =0,05, OR =0,338, 95%CI 0,158–0,723) and in dominant model (р =0,02, OR =0,284, CI 0,126–0,638). None of the polymorphisms of the studied genes was associated with total IgE levels. Conclusions. This is the first report on the association of rs6737848 SOCS5 with asthma.

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Association between PXR polymorphisms and cancer risk: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20171614 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 3

Author(s):

Jing Wen ◽

Zhi Lv ◽

Hanxi Ding ◽

Xinxin Fang ◽

Mingjun Sun

Keyword(s):

Cancer Risk ◽

Meta Analysis ◽

Pregnane X Receptor ◽

Recessive Model ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Case Control Studies ◽

Single Nucleotide ◽

Novel Biomarkers ◽

Risk Of Cancer

Current studies have explored the correlation between the single nucleotide polymorphisms (SNPs) of pregnane X receptor (PXR) and cancer risk. However, the findings were conflicting. Hence, we performed a comprehensive review and meta-analysis for these researches to determine the effect of PXR polymorphisms on the risk of cancer. Eligible publications were collected based on a series of rigorous inclusion and exclusion criteria. In consequence, a total of eight case–control studies (from seven citations) covering 11143 cases and 12170 controls were involved in a meta-analysis of ten prevalent PXR SNPs (rs10504191 G/A, rs3814058 C/T, rs6785049 A/G, rs1464603 A/G, rs1523127 A/C, rs2276706 G/A, rs2276707 C/T, rs3732360 C/T, rs3814055 C/T, rs3814057 A/C). The correlations between PXR SNPs and cancer risk were estimated by odds ratios (ORs) with their 95% confidence intervals (95%CIs). The findings demonstrated that rs3814058 polymorphism (CT compared with CC: pooled OR = 1.280, P=6.36E-05; TT compared with CC: pooled OR = 1.663, P=2.40E-04; dominant model: pooled OR = 1.382, P=2.58E-08; recessive model: pooled OR = 1.422, P=0.002; T compared with C: pooled OR = 1.292, P=6.35E-05) and rs3814057 polymorphism (AC compared with AA: pooled OR = 1.170, P=0.036; dominant model: pooled OR = 1.162, P=0.037) were associated with the risk of overall cancer. In stratified analyses, rs3814058 polymorphism was revealed to increase the cancer risk in lung cancer subgroup. In summary, this meta-analysis indicates that the rs3814057 and rs3814058 polymorphisms of PXR gene play crucial roles in the pathogenesis of cancer and may be novel biomarkers for cancer-forewarning in overall population or in some particular subgroups.

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The KIAA0319 Gene Polymorphisms are Associated with Developmental Dyslexia in Chinese Uyghur Children

10.1101/034660 ◽

2015 ◽

Author(s):

Hua Zhao ◽

Xiang Peng Zuo ◽

Ping Bao Zhang ◽

Yun Chen

Keyword(s):

Developmental Dyslexia ◽

Gene Polymorphisms ◽

Additive Model ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Linkage Disequilibrium Analysis ◽

Bonferroni Correction ◽

Single Nucleotide ◽

Increased Risk ◽

Uyghur Population

To investigate the association of KIAA0319 gene polymorphisms and developmental dyslexia in individuals of Uyghurian descent. Eighteen single nucleotide polymorphisms (SNP) of gene KIAA0319 were screened in a group of 196 patients with dyslexia and 196 controls of Uyghur descent by determined the genotypes using a custom-by-design 48-Plex SNPscan™ Kit. SAS 9.1.3 software were used for data analysis. Seven SNPs(Pmin=0.001) of KIAA0319 have significant differences between the cases and controls under specific genotype models. Especially for rs6935076(Padjusted=0.020 under dominant model;Padjusted=0.028 under additive model) and rs3756821(Padjusted=0.021 under additive model), which still associated with dyslexia after Bonferroni correction. The linkage disequilibrium analysis showed four block within gene KIAA0319 and only the ten-maker haplotype(P=0.013) in block 4 was significantly more common in dyslexia children than in controls. The results indicated that genetic polymorphisms of KIAA0319 are associated with increased risk of developmental dyslexia in Uyghur population.

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Investigation of the association between obesity and insulin-induced gene 1 polymorphism at 7q36.3 region in Uygur population in Xinjiang, China

Bioscience Reports ◽

10.1042/bsr20190498 ◽

2019 ◽

Vol 39 (12) ◽

Author(s):

Jing Tao ◽

Mayila Abudoukelimu ◽

Xin Shen ◽

Jun Liu ◽

Feng-xia Wang ◽

...

Keyword(s):

Metabolic Diseases ◽

Recessive Model ◽

Primary Objective ◽

Obese Patients ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Heritable Trait ◽

Increased Risk ◽

Control Study

Abstract Background: Obesity is a common heritable trait and a major risk factors of chronic and metabolic diseases. Insulin-induced gene 1 (INSIG1) is known to play important roles in cholesterol and triacylglycerol (TAG) metabolism. In the present study, our primary objective was to explore whether the single nucleotide polymorphisms (SNPs) in INSIG1 gene were associated with obesity in Uygur subjects, in Xinjiang, China. Methods: We designed a case–control study including 516 obese patients and 463 age- and sex-matched control subjects. Three SNPs (rs2721, rs9767875 and rs9719268) were genotyped using TaqMan SNP genotyping assays. Results: For rs2721, the distribution of genotypes, dominant model (GT + TT vs GG), recessive model (TT vs GT + GG) showed significant differences between obese patients and the controls (P = 0.008, P = 0.005 and P = 0.035, respectively). For rs9719268, the distribution of genotypes showed significant differences between obese patients and the controls (P = 0.004). The dominant model (GT + TT vs GG) of rs2721 and rs9719268 GT genotype remain significantly associated with obesity after adjustment for confounders (OR = 1.393, 95% CI = 1.047–1.853, P = 0.023; OR = 1.631, 95% CI = 1.059–2.512, P = 0.026). The TG levels were significantly higher in rs2721 GT/TT genotypes than that in GG genotypes (P<0.05). Conclusions: Rs2721 and rs9719268 of INSIG1 gene are associated with obesity in Uygur subjects. Subjects with GT/TT genotype or T allele of rs2721 and GT genotype of rs9719268 were associated with an increased risk of obesity.

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Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

European Journal of Ophthalmology ◽

10.1177/11206721211002698 ◽

2021 ◽

pp. 112067212110026

Author(s):

Pablo Gili ◽

Leyre Lloreda Martín ◽

José-Carlos Martín-Rodrigo ◽

Naon Kim-Yeon ◽

Laura Modamio-Gardeta ◽

...

Keyword(s):

Macular Degeneration ◽

Gene Polymorphisms ◽

Age Related Macular Degeneration ◽

Spanish Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exudative Amd ◽

Age Related ◽

Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

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