scholarly journals Evaluating the association of TRPA1 gene polymorphisms with pain sensitivity: a protocol for an adaptive recall by genotype study

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Aidan P. Nickerson ◽  
Laura J. Corbin ◽  
Nicholas J. Timpson ◽  
Keith Phillips ◽  
Anthony E. Pickering ◽  
...  
Keyword(s):  
Pain Sensitivity ◽  
Transient Receptor Potential ◽  
Association Studies ◽  
Test Group ◽  
Receptor Potential ◽  
Control Group ◽  
Genome Wide Association Studies ◽  
Early Assessment ◽  
Current Test ◽  
Minor Alleles

Abstract Background Pain is a complex polygenic trait whose common genetic underpinnings are relatively ill-defined due in part to challenges in measuring pain as a phenotype. Pain sensitivity can be quantified, but this is difficult to perform at the scale required for genome wide association studies (GWAS). Existing GWAS of pain have identified surprisingly few loci involved in nociceptor function which contrasts strongly with rare monogenic pain states. This suggests a lack of resolution with current techniques. We propose an adaptive methodology within a recall-by-genotype (RbG) framework using detailed phenotyping to screen minor alleles in a candidate ‘nociceptor’ gene in an attempt to estimate their genetic contribution to pain. Methods/design Participants of the Avon Longitudinal Study of Parents and Children will be recalled on the basis of genotype at five common non-synonomous SNPs in the ‘nociceptor’ gene transient receptor potential ankylin 1 (TRPA1). Those homozygous for the common alleles at each of the five SNPs will represent a control group. Individuals homozygous for the minor alleles will then be recruited in a series of three sequential test groups. The outcome of a pre-planned early assessment (interim) of the current test group will determine whether to continue recruitment or switch to the next test group. Pain sensitivity will be assessed using quantitative sensory testing (QST) before and after topical application of 10% cinnamaldehyde (a TRPA1 agonist). Discussion The design of this adaptive RbG study offers efficiency in the assessment of associations between genetic variation at TRPA1 and detailed pain phenotypes. The possibility to change the test group in response to preliminary data increases the likelihood to observe smaller effect sizes relative to a conventional multi-armed design, as well as reducing futile testing of participants where an effect is unlikely to be observed. This specific adaptive RbG design aims to uncover the influence of common TRPA1 variants on pain sensation but can be applied to any hypothesis-led genotype study where costly and time intensive investigation is required and / or where there is large uncertainty around the expected effect size. Trial registration: ISRCTN, ISRCTN16294731. Retrospectively registered 25th November 2021.

scholarly journals Meningeal transient receptor potential channel M8 activation causes cutaneous facial and hindpaw allodynia in a preclinical rodent model of headache

Cephalalgia ◽  
2015 ◽  
Vol 36 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Carolina C Burgos-Vega ◽  
David Dong-Uk Ahn ◽  
Christina Bischoff ◽  
Weiya Wang ◽  
Dan Horne ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Association Studies ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Behavioral Model ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Cutaneous Allodynia ◽  
Transient Receptor

Background Migraine headache is a neurological disorder affecting millions worldwide. However, little is known about the mechanisms contributing to migraine. Recent genome-wide association studies have found single nucleotide polymorphisms in the gene encoding transient receptor potential channel M8. Transient receptor potential channel M8 is generally known as a cold receptor but it has been implicated in pain signaling and may play a role in migraine pain. Methods In order to investigate whether transient receptor potential channel M8 may contribute to the pain of migraine, the transient receptor potential channel M8 activator icilin was applied to the dura mater using a rat behavioral model of headache. Cutaneous allodynia was measured for 5 hours using Von Frey filaments. Results : Dural application of icilin produced cutaneous facial and hind paw allodynia that was attenuated by systemic pretreatment with the transient receptor potential channel M8-selective antagonist AMG1161 (10 mg/kg p.o.). Further, the anti-migraine agent sumatriptan (0.6 mg/kg s.c.) or the non-selective NOS inhibitor L-NAME (20 mg/kg i.p.) also attenuated allodynia when given as a pretreatment. Conclusions These data indicate that transient receptor potential channel M8 activation in the meninges produces behaviors in rats that are consistent with migraine and that are sensitive to pharmacological mechanisms known to have efficacy for migraine in humans. The findings suggest that activation of meningeal transient receptor potential channel M8 may contribute to the pain of migraine.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

The Action of Shenmai Injection on the Inflammation and Proliferation of Smooth Muscle Cells of the Airway in Asthmatic Rats

2021 ◽  
Vol 11 (3) ◽  
pp. 386-391
Author(s):  
He Zhu ◽  
Yali Guo ◽  
Xiaoli Wang ◽  
Min Zhu ◽  
Jiahui Lei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Muscle Cells ◽  
Interleukin 4 ◽  
Nuclear Antigen ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Shenmai Injection

To observe the effect of transient receptor potential ankyrin 1 (TRPA1) channel on the proliferation and inflammation of airway smooth muscle cells (SMC) in asthmatic rats, the rats were randomly allocated into three treatment groups: control, asthma, and Shenmai injection (SMI), with 15 rats in each group. Asthmatic rat models were induced by ovalbumin (OVA) inhalation. Rats in the control and asthma groups were intraperitoneally injected 2 mL NS daily, whereas rats in the SMI treatment group were intraperitoneally injected with 2 mL SMI daily. RT-qPCR and western blotting were used to test for TRPA1 and proliferating cell nuclear antigen (PCNA) mRNA and protein expression. ELISA was used to test the expression of interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) in the serum. Compared with the control group, there were significantly higher levels of TRPA1 and PCNA mRNA and protein, as well as of IL-4, IL-5, and IL-13 in asthmatic rats (P< 0.05). After SMI treatment, there was significantly lower expression of TRPA1, PCNA, IL-4, IL-5, and IL-13 compared to the levels in asthmatic rats (P < 0.05). TRPA1, IL-4, IL-5, and IL-13 were highly expressed in the tracheal SMC of asthmatic rats. Inhibiting TRPA1, IL-4, IL-5, and IL-13 using SMI may be one of the mechanisms that can intervene chronic airway inflammation and asthma proliferation.

Abstract 115: Reduction of Trpv1 Activity in Aortic Baroreceptor Neurons in Diabetic Neuropathy: Role of Brain-derived Neurotrophic Factor

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Yingying Tan ◽  
Qi Zhang
Keyword(s):  
Diabetic Neuropathy ◽  
Transient Receptor Potential ◽  
Kinase Inhibitor ◽  
Receptor Potential ◽  
Diabetic Rats ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Peak Current Density ◽  
Inward Current ◽  
Pre Treatment

It has been well documented that diabetes mellitus is associated with cardiovascular autonomic neuropathy including dysfunction of arterial baroreflex. The mechanisms underlying diabetes-induced baroreflex dysfunction remain poorly understood. Here we investigated the function and expression of transient receptor potential vanilloid 1 (TRPV1) in aortic baroreceptor (AB) neurons isolated from streptozotocin-induced diabetic rats between 4 and 8 weeks after onset of diabetes. AB neurons in nodose ganglion were retrograde-labeled by a transported fluorescent dye, Dil. Using the whole-cell patch clamp, we found that the inward current activated by the application of capsaicin (1 μM) was significantly smaller in AB neurons from diabetic rats compared with controls. The mean peak current density of capsaicin-induced currents was 145.7 ± 24.7 pA/pF (n = 16) in diabetic neurons and 269.3 ± 31.8 pA/pF (n =15) in controls, respectively. The duration of inward current was decreased 51% in diabetic rats compared with the control group. These evoked currents were completely blocked by the capsaicin antagonist capsazepine. In addition, capsaicin-induced desensitization of TRPV1 was up-regulated, whereas TRPV1 re-sensitization was down-regulated in AB neurons from diabetic rats. Immunofluorescence staining studies demonstrated that the percentage of TRPV1-positive neurons was 50.2 ± 5.0% in control rats and 38.2 ± 1.9% in diabetic rats, respectively. This reduction in TRPV1-positive neurons in AB neurons in diabetic rats was significant (n = 11, P < 0.01). In addition, the reductions in TRPV1 currents and positive neurons s in diabetic rats were normalized by pre-treatment with anti-BDNF antibody or K252a, a TrkB tyrosine kinase inhibitor. Furthermore, incubation with BDNF caused a large reduction in TRPV1 currents in AB neurons from control rats, and the number of AB neurons with BDNF immunoreactivity was greater in diabetic than control rats. These results suggest that reduced expression and function of TRPV1 are involved in the attenuation of baroreceptor neuron excitability, and increased BDNF activity in these neurons likely contributes to the reduction in TRPV1 function through TrkB receptor stimulation in diabetic neuropathy.

Identification of two genes as novel susceptibility loci for type 2 diabetes mellitus in Japanese

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oguri ◽  
K Kato ◽  
H Horibe ◽  
T Fujimaki ◽  
J Sakuma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Association Studies ◽  
East Asian ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Asian Populations ◽  
Genome Wide ◽  
Minor Alleles

Abstract Background The heritability of Type 2 diabetes mellitus (T2DM) has been estimated to be 50% to 60%. Although genome-wide association studies identified &gt;120 loci that confer susceptibility to T2DM, these studies were commonly conducted in a cross-sectional manner. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to T2DM in Japanese. We have now performed longitudinal exome-wide association studies (EWASs) to identify novel loci for T2DM by examining temporal changes in fasting plasma glucose (FPG) level, blood hemoglobin A1c (HbA1c) content, and the prevalence of T2DM. Methods Longitudinal EWASs (mean follow-up period, 5 years) were performed with Illumina Human Exome-12 v1.2 DNA Analysis BeadChip or Infinium Exome-24 v1.0 BeadChip arrays and with 6,022 Japanese (755 subjects with T2DM, 5267 controls). The relation of genotypes of 24,579 SNPs that passed quality control to FPG level, blood HbA1c content, or the prevalence of T2DM was examined with the generalized estimating equation (GEE). To compensate for multiple comparisons of genotypes with each of the three parameters, we applied Bonferroni's correction for statistical significance of association. Results Longitudinal EWASs (GEE with adjustment for age, sex, body mass index, and smoking) revealed that rs6414624 of EVC (P&lt;2.0×10–16 for T2DM, P=9.1×10–11 for FPG), rs78338345 of GGA3 (P&lt;2.0×10–16 for T2DM, P=4.3×10–9 for FPG), rs10490775 of PTPRG (P&lt;2.0×10–16 for T2DM, P=3.3×10–7 for FPG), and rs61739510 of GLT6D1 (P&lt;2.0×10–16 for T2DM, P=5.8×10–7 for FPG) were significantly associated with the prevalence of T2DM and FPG levels; and rs11558471 in SLC30A8 with FPG level (P=1.8×10–8) and blood HbA1c content (P=1.2×10–7). After examination of the relation of identified SNPs to FPG level and blood HbA1c content, linkage disequilibrium of the SNPs, and results of the previous genome-wide association studies, we identified rs6414624 of EVC and rs78338345 of GGA3 as novel susceptibility loci for T2DM. In the identified SNPs (rs6414624 and rs7833834), FPG level, blood HbA1c content, and the prevalence of T2DM were significantly lower in homozygotes with the minor alleles than in homozygotes with the major alleles or heterozygotes. These results suggest that the minor alleles of rs6414624 and rs78338345 are protective against T2DM in Japanese. According to allele frequency data from the 1000 Genomes Project database, the minor G allele of rs78338345 of GGA3 is specifically distributed in East Asia. This suggests that the minor allele frequency may have increased in East Asian populations after the split of East Asian and non-East Asian populations. Conclusion We have newly identified EVC and GGA3 as susceptibility loci for T2DM in Japanese. Determination of genotypes for these SNPs at these loci may prove informative for assessment of the genetic risk for T2DM in Japanese. Funding Acknowledgement Type of funding source: None

scholarly journals Antinociceptive Effects of Emodin on CFA-Induced Inflammatory Pain in Rats

2020 ◽  
Vol 15 (7) ◽  
pp. 1934578X2094200
Author(s):  
Wan Ni ◽  
Nianyun Wang ◽  
Shenglan Tian ◽  
Qingbang Xu
Keyword(s):  
Mrna Expression ◽  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Interleukin 1 ◽  
Receptor Potential ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Tnf Α ◽  
Transient Receptor

The effect of emodin on complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats and its potential molecular mechanism was investigated. For this, a rat model of inflammatory pain induced by CFA was established and rats were treated with emodin by intraperitoneal injection. The pain threshold was evaluated by the von Frey, thermo hyperalgesia, and cold plate tests. The mRNA expression of transient receptor potential channel ankyrin type-1 ( Trpa1) and transient receptor potential vanilloid 1 ( Trpv1) was detected by quantitative reverse transcription polymerase chain reaction, and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The mechanical and thermal pain thresholds of CFA-treated rats were significantly lower than those of the control rats, while the paw withdrawal responses in response to cold stimulation were higher than that of the control group. Emodin treatment significantly improved CFA-induced hyperalgesia. Further results showed that emodin inhibits the upregulation of Trpa1 and Trpv1 mRNA expression in the dorsal root ganglion (DRG) of rats with inflammatory pain compared with the control group. Emodin also significantly reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in the serum of rats with inflammatory pain. Thus, emodin may inhibit hyperalgesia induced by inflammatory stimulation by downregulating the mRNA expression of Trpa1 and Trpv1 in DRG neurons and reducing the levels of TNF-α, IL-1β, and IL-6.

1267Relationship between polymorphism of ADRA2B gene and primary cardiac conduction disorders

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Chernova ◽  
S Nikulina ◽  
V Shulman ◽  
M Voevoda ◽  
V Maksimov
Keyword(s):  
Association Studies ◽  
Receptor Gene ◽  
Treatment Options ◽  
Genetic Material ◽  
Rare Allele ◽  
Molecular Networks ◽  
Cardiac Conduction ◽  
Control Group ◽  
Genome Wide Association Studies ◽  
Clinical Genetic

Abstract Background Cardiac conduction system (CCS) disease resulting in disrupted conduction and impaired cardiac rhythm is common with significant morbidity and mortality. Current treatment options are limited and rational efforts to develop cell-based and regenerative therapies require knowledge in molecular networks that establish and maintain CCS function. Recent genome-wide association studies (GWAS) have identified numerous loci associated with adult human CCS function, including ADRA2B.   Materials and methods A family examination was performed for 71 patients with atrioventricular block (AVB). The control group was formed by 657 patients without clinical ECG manifestations of cardiac diseases. All the examinees underwent ECG, echocardioscopy, electrophysiological examination of the heart.  Results by results of research, it has been established that the frequency of carriers of a homozygous genotype on rare allele (DD) among patients with AVB (43.7%±5.9) was higher in comparison with the controls (16%±1.4). The obvious tendency to decrease in carriers of a heterozygous genotype (ID) among patients with AVB (23.9%±5.1) in comparison with the control group (51.1%±2.0) has also been noted.  Conclusions  In this work, we revealed association between hereditary disturbances of cardiac conduction and polymorphism of 2-adrenergic receptor gene using clinical - genetic material for the first time. Genotypes: AVB (n = 71) Control group (n = 657) р n %±m n %±m II 23 32,4 ± 5,6 216 32,9 ± 1,8 р&gt;0,05 ID 17 23,9 ± 5,1 336 51,1 ± 2,0 р&lt;0,001 DD 31 43,7 ± 5,9 105 16 ± 1,4 р&lt;0,001 Allels: Allel I 63 32,9 ± 1,8 768 58,4 ± 1,4 р&lt;0,001 Allels D 79 51,1 ± 2,0 546 41,6 ± 1,4 р&lt;0,001 ОR; 95% CI OR 1,764;1,244-2,5 Genotype II 23 32,4 ± 5,6 216 32,9 ± 1,8 р&gt;0,05 Genotypes ID + DD 48 67,6 ± 5,6 441 67,1 ± 1,8 р&gt;0,05 ОR; 95% CI OR 0,978;0,58-1,65

scholarly journals Association of ankylosing spondylitis activity indicators in a Russian population of patients with STAT4 rs7574865 gene polymorphism

2019 ◽  
Vol 13 (2) ◽  
pp. 55-60
Author(s):  
M. Yu. Krylov ◽  
A. S. Starkova ◽  
E. Yu. Samarkina ◽  
T. V. Dubinina ◽  
Sh. F. Erdes
Keyword(s):  
Ankylosing Spondylitis ◽  
Gene Polymorphism ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Topoisomerase I ◽  
Association Studies ◽  
Russian Population ◽  
Control Group ◽  
Genome Wide Association Studies ◽  
Hla B27

Family and twin studies have shown that ankylosing spondylitis (AS) has a hereditary nature that is based on a strong association with the leukocyte antigen HLA-B27. However, only 1–5% of HLA-B27 carriers develop AS, which indicates that there are other genetic markers involved in the formation of a predisposition to this disease. A number of genome-wide association studies have convincingly confirmed the role of the STAT4 gene. This gene encodes the protein – the signal transducer and activator of transcription (STAT) protein, which is a predisposing factor for the development of many autoimmune diseases. There are not so many studies of the relationship of STAT4 polymorphisms to the predisposition to AS, and there are no these studies regarding the Russian population.Objective: to study whether there is a possible association of STAT4 rs7574865 gene polymorphism with the predisposition to AS and to assess the activity of this disease using BASDAI and ASDAS scores in the Russian patient population.Patients and methods. A cohort of 203 individuals, including 100 patients (79 men and 21 women) with AS, and 103 healthy volunteers (a control group) was surveyed. Age, gender, duration, and specific features of AS onset, ESR, and CRP levels were assessed. BASDAI and ASDAS scores were calculated to evaluate disease activity.Results and discussion. There was a significant relationship between STAT4 polymorphism and C-reactive protein (CRP) levels and BASDAI and ASDAS-CRP scores. The TT genotype carriers had significantly higher mean activity indices compared to the GG (p=0.001) and GT (p=0.005) genotype carriers for CRP, BASDAI (p=0.0001 and p=0.009, respectively) and ASDAS-CRP (p=0.009 and p=0.001, respectively). High disease activity (BASDAI >4 and ASDAS-CRP >3.5) was also associated with the high frequency of the T allele (p=0.046 and p=0.004, respectively). The value of STAT4 rs7574865 gene polymorphism in the pathogenesis of autoimmune diseases is confirmed by a study in which the T allele in STAT4 rs7574865 enhances mRNA transcription and protein expression. Italian authors have shown that there is a relationship between the minor T allele of rs7574865 and the high risk of arthritis. We have previously established a relationship between the T allele and the predisposition to diffuse systemic scleroderma, interstitial lung damage, and elevated anti-topoisomerase I antibody levels.Conclusion. The present study has shown for the first time a significant association of STAT4 rs7574865 polymorphism with the main AS activity indicators: CRP levels, BASDAI and ASDAS-CRP scores. The studied polymorphism may be a new genetic marker for predicting the severity of AS. 

scholarly journals Polymorphisms of AZIN1 rs2679757 and TRPM5 rs886277 are Associated with Cirrhosis Risk in Chinese Patients with Chronic Hepatitis B

2012 ◽  
Vol 1 (2) ◽  
pp. 103-109
Author(s):  
Li-jun Peng ◽  
Jin-sheng Guo ◽  
Zhe Zhang ◽  
Li-li Liu ◽  
Yi-rong Cao ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Transient Receptor Potential ◽  
Association Studies ◽  
Chinese Patients ◽  
Candidate Snps ◽  
Progression Rate ◽  
Genome Wide Association Studies ◽  
Genotype Frequencies

Abstract Objective Genome-wide association studies (GWAS) have linked many single nucleotide polymorphisms (SNPs) to the outcomes of a variety of liver diseases. The aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese population. Methods A total of 714 Chinese participants with persistent HBV infection were studied. Patients were divided into cirrhotic (n = 429) and non-cirrhotic (n = 285) groups based on clinical and pathological evidence. The progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score system. Genotypes of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic subjects. The association between the risk of SNPs and the severity and progression rate of cirrhosis was further analyzed. Results Rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene and Rs886277 in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) were found to be associated with cirrhosis risk in CHB. They were also correlated with the overall severity and progression rate of cirrhosis. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. Conclusions AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese patients. The emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups, and merit mechanistic studies to reveal their roles in fibrosis progression.

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