Effects of genetic variations within goat PITX2 gene on growth traits and mRNA expression

Abstract Background The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa. Methods We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes. Results We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06–3.22, P = 0.03) in meta-analysis of validation cohorts. Conclusion We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.

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Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection

Journal of General Virology ◽

10.1099/vir.0.042572-0 ◽

2012 ◽

Vol 93 (8) ◽

pp. 1717-1724 ◽

Cited By ~ 28

Author(s):

Alexandra Svensson ◽

Petra Tunbäck ◽

Inger Nordström ◽

Leonid Padyukov ◽

Kristina Eriksson

Keyword(s):

Mrna Expression ◽

Mononuclear Cells ◽

Human Herpesvirus ◽

Genetic Variations ◽

Natural Resistance ◽

Toll Like Receptor ◽

Peripheral Blood Mononuclear ◽

Tlr3 Mrna ◽

The Impact ◽

Hsv 1

Lack of Toll-like receptor 3 (TLR3) functional activity predisposes children to human herpesvirus 1 (HSV-1) encephalitis. In this study, we have investigated whether there is any link between TLR3 and adult HSV-2 infection by studying genetic variations in TLR3. The frequency of four single-nucleotide polymorphisms (SNPs) in the TLR3 gene in 239 patients with genital HSV-2 infection and 162 healthy controls, as well as the impact of these variants on TLR3 gene-expression levels, were compared. Two SNPs in the TLR3 gene (rs13126816 and rs3775291) were associated with a reduced incidence of HSV-2 infection. The minor allelic variants at both rs13126816 and rs3775291 were more common among healthy HSV-2-seronegative subjects than among HSV-2-infected individuals. This was even more apparent in HSV-1-seronegative individuals. There was, however, no association between any of the four TLR3 SNPs and HSV-2 disease severity, as they were expressed at similar proportions in asymptomatic and symptomatic HSV-2-infected patients alike. Furthermore, when assessing TLR3 mRNA expression in a limited number of HSV-2-infected individuals, we found that individuals carrying the homozygous genotypes for the minor alleles had significantly higher levels of TLR3 mRNA expression in peripheral blood mononuclear cells in response to HSV-2 stimulation than individuals that were homozygous for the major allele variants. Taken together, these results suggest that genetic variations in TLR3 may affect the susceptibility to HSV-2 infection in humans.

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The Association of Genetic Variations in the Promoter Region ofMyostatinGene with Growth Traits in Duroc Pigs

Animal Biotechnology ◽

10.1080/10495398.2012.709205 ◽

2012 ◽

Vol 23 (4) ◽

pp. 291-298 ◽

Cited By ~ 11

Author(s):

Po-An Tu ◽

Jen-Wen Shiau ◽

Shih-Torng Ding ◽

En-Chung Lin ◽

Ming-Che Wu ◽

...

Keyword(s):

Promoter Region ◽

Growth Traits ◽

Genetic Variations

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Genetic polymorphisms and DNA methylation in exon 1 CpG-rich regions of PACAP gene and its effect on mRNA expression and growth traits in half smooth tongue sole (Cynoglossus semilaevis)

Fish Physiology and Biochemistry ◽

10.1007/s10695-015-0147-5 ◽

2015 ◽

Vol 42 (2) ◽

pp. 407-421 ◽

Cited By ~ 3

Author(s):

Yufeng Si ◽

Feng He ◽

Haishen Wen ◽

Jifang Li ◽

Junli Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Mrna Expression ◽

Genetic Polymorphisms ◽

Growth Traits ◽

Cynoglossus Semilaevis ◽

Tongue Sole ◽

Exon 1 ◽

Half Smooth Tongue Sole

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The PLAG1 mRNA expression analysis among genetic variants and relevance to growth traits in Chinese cattle

Animal Biotechnology ◽

10.1080/10495398.2019.1632207 ◽

2019 ◽

Vol 31 (6) ◽

pp. 504-511

Author(s):

Ze Li ◽

Mingli Wu ◽

Haidong Zhao ◽

Lujie Fan ◽

Yu Zhang ◽

...

Keyword(s):

Mrna Expression ◽

Expression Analysis ◽

Genetic Variants ◽

Growth Traits ◽

Chinese Cattle ◽

Mrna Expression Analysis

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The novel 22 bp insertion mutation in a promoter region of the <i>PITX2</i> gene is associated with litter size and growth traits in goats

Archives Animal Breeding ◽

10.5194/aab-61-329-2018 ◽

2018 ◽

Vol 61 (3) ◽

pp. 329-336 ◽

Cited By ~ 4

Author(s):

Hailong Yan ◽

Enhui Jiang ◽

Haijing Zhu ◽

Linyong Hu ◽

Jinwang Liu ◽

...

Keyword(s):

Litter Size ◽

Body Length ◽

Promoter Region ◽

Growth Traits ◽

Critical Role ◽

The Body ◽

Insertion Mutation ◽

The Novel ◽

Indel Mutation ◽

Pitx2 Gene

Abstract. The paired-like homeodomain 2 (PITX2) gene plays a critical role in regulating development, reproduction, and growth traits in ruminants. Hence, the objective of this study was to explore the polymorphisms of this gene and to evaluate their associations with quantitative traits. Herein, a novel insertion in the promoter region of the PITX2 gene was reported in Shaanbei white cashmere (SBWC) goats (n=1012). The genotype distributions between mothers of single-kid and multi-kid groups within SBWC goats were significantly different (P<0.01), implying that this indel mutation might affect the litter size. Furthermore, association analysis found that this indel mutation was significantly associated with litter size (P=0.001). Individuals with genotype DD had a significantly smaller litter size than those with other genotypes (P<0.01). Besides, this indel was significantly associated with the body length (P=0.042) and the chest width (P=0.031). Especially, the individuals with genotype DD had a significantly lower body length than those with genotype II (P<0.05), which was consistent with the trend in litter size. These findings suggested that the new 22 bp indel mutation within the PITX2 gene is significantly associated with litter size and growth traits; this can be utilized as a functional molecular marker in goat breeding.

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Tetra-primer ARMS-PCR identifies the novel genetic variations of bovine HNF-4α gene associating with growth traits

Gene ◽

10.1016/j.gene.2014.06.014 ◽

2014 ◽

Vol 546 (2) ◽

pp. 206-213 ◽

Cited By ~ 7

Author(s):

Zi-nian Wang ◽

Mi-jie Li ◽

Xian-yong Lan ◽

Ming-xun Li ◽

Chu-zhao Lei ◽

...

Keyword(s):

Growth Traits ◽

Genetic Variations ◽

The Novel ◽

Arms Pcr

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Effect of Genetic Variations of the POU1F1 Gene on Growth Traits of Nanyang Cattle

Acta Genetica Sinica ◽

10.1016/s0379-4172(06)60124-8 ◽

2006 ◽

Vol 33 (10) ◽

pp. 901-907 ◽

Cited By ~ 14

Author(s):

Kai XUE ◽

Hong CHEN ◽

Shan WANG ◽

Xin CAI ◽

Bo LIU ◽

...

Keyword(s):

Growth Traits ◽

Genetic Variations ◽

Pou1f1 Gene

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Association of genetic variations in PTPN2 and CD122 with ocular Behcet’s disease

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310820 ◽

2018 ◽

Vol 102 (7) ◽

pp. 996-1002 ◽

Cited By ~ 2

Author(s):

Qi Zhang ◽

Hua Li ◽

Shengping Hou ◽

Hongsong Yu ◽

Guannan Su ◽

...

Keyword(s):

Mrna Expression ◽

Behçet’S Disease ◽

Behcet’S Disease ◽

Mononuclear Cells ◽

Behçet's Disease ◽

Genetic Variations ◽

Janus Kinase ◽

Behcet's Disease ◽

Pathergy Test ◽

Significant Difference

BackgroundProtein tyrosine phosphatases (PTPs) play critical roles in human autoimmunity. Previous studies found that PTPN2 may be the key regulatory factor in the T-cell-mediated immune response. PTPN2 regulates the Janus kinase/signal transducers and activators of transcription pathway by inhibiting signalling via the interleukin (IL)-2 receptor (CD122). An association between genetic variations in PTPN2 and CD122 with ocular Behcet’s disease (BD) has not yet been addressed and was therefore the purpose of this study.MethodsA two-stage case–control study was performed in 906 patients with ocular BD and 2178 healthy controls. Genotyping analysis of 11 single nucleotide polymorphisms was carried out. The expression of PTPN2 in peripheral blood mononuclear cells (PBMCs) was quantified by real-time PCR and cytokine production was measured by ELISA.ResultsThe frequency of the GG genotype of PTPN2-rs7234029 was significantly lower in patients with ocular BD (p=1.94×10−5, pc=8.34×10−4, OR=0.466). Stratification according to gender showed that rs7234029 was significantly associated with BD in men. A stratified analysis according to the main clinical features showed that rs7234029 was significantly associated with genital ulcers, skin lesions and a positive pathergy test. No association could be detected between BD and CD122 gene polymorphisms. Functional studies showed that rs7234029 GG genotype carriers had a higher PNPT2 mRNA expression level than those which carrying the AA or AG genotype, and a decreased secretion of IL-17 and tumour necrosis factor-alpha was seen by PBMCs from GG carriers. No significant difference could be detected concerning IL-1β or IL-6 production by stimulated PBMCs between the different genotype groups.ConclusionsThis study shows that a PTPN2-rs7234029 polymorphism is associated with ocular BD and is strongly influenced by gender. In addition, our results suggest that the genetic association with PTPN2 may involve the regulation of PTPN2 mRNA expression and cytokine secretion.

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