Rs12979860 Polymorphism Research Articles

Single nucleotide polymorphisms Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Single nucleotide polymorphisms Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Single nucleotide polymorphisms Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 role in increasing everolimus toxicity in metastatic breast cancer

Breast cancer is one of the most devastating diseases in the world, the most diffused cancer in women. Despite the incredible progress made in the field, the mortality rate in the metastatic setting is still quite high. Among the different drugs used to treat this disease, the mTOR inhibitor everolimus is one of the most promising ones, that has been approved to be used together with exemestane in the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole, following the encouraging results coming from BOLERO-2 clinical trial showing a significant increase in progression-free-survival of patients compared to patients treated with exemestane and placebo. In this article we will discuss how the toxicity of this drug could be increased with Rs1045642 C>T genetic alteration in ATP Binding Cassette Subfamily B Member 1 (ABCB1), a pump that expels this drug from the cells, leading to a more inactive ABCB1. With an inactivation of ABCB1 more everolimus would linger within the cancer cells, exerting more of its anti-tumor work. Future diagnosis of genetic alteration of Rs1045642 C>T in ABCB1 could be pivotal for determining if patients would benefit more from everolimus.

Association between Hepatitis C Virus Viremia and the rs12979860, rs2228145 and rs1800795 SNP (CT/AC/GG) Genotype in Saudi Kidney Transplant Recipients.

Background:Hepatitis C virus (HCV) is a major health problem, particularly in high-risk groups such as kidney transplant recipients, where it can adversely affect graft survival and increase the relative risk for mortality. Recently, the role of genetic variation among HCV patients in determining the outcome of infections has been under investigation.Objective:To investigate the association of single-nucleotide polymorphisms (SNPs) rs12979860 (located within the interleukin-28B locus), rs2228145 (interleukin-6 receptor) and rs1800795 (interleukin-6 promoter) with HCV viremia in renal transplant patients.Materials and Methods:In this analytical cross-sectional study, 149 kidney transplant recipients, 82 males (median age: 41 years) and 67 females (median age: 45 years), were screened for HCV RNA in blood using real-time polymerase chain reaction and genotyped by sequencing (rs12979860) and restriction fragment length polymorphism (rs2228145 and rs1800795).Results:HCV RNA was detected in 17 (11.41%) of the 149 patients. There was no statistically significant association between the studied SNPs and HCV viremia. However, a combination of the CT/AC/GG genotype was significantly associated with HCV viremia (odds ratio: 5.4). The genotype AA of rs2228145 in the IL-6 receptor was associated with viremia levels of >105 copies/ml (odds ratio: 5.96).Conclusion:To the best of the authors' knowledge, this is the first study that has shown that the CT/AC/GG genotype has an impact on HCV viremia in kidney transplant patients. Therefore, such SNP genotypes may potentially be used to identify transplant patients at risk of HCV infection.

Investigation of Interaction between Vitamin D Receptor Gene Polymorphisms and Environmental Factors in Early Childhood Caries in Chinese Children.

Background Early childhood caries is a multifactorial disease involving interactions between genetic and environmental risk factors. The aim of this study was to examine the effects of vitamin D receptor (VDR) gene polymorphisms and gene-environment interactions on the etiology of, and susceptibility to, caries in Chinese children aged 3–5 years. Methods Children (n = 549) were divided into three groups according to caries risk: high (decayed, missing, filled teeth (dmft) index > 4; n = 148), moderate (dmft = 1–4; n = 156), and caries-free (n = 245). A questionnaire was designed to collect demographic information, dietary habits, and oral hygiene practices, and dental plaque samples were collected to test acidogenic activity of bacteria. Genomic DNA was extracted from the buccal mucosa, and the VDR polymorphisms rs7975232, rs1544410, rs11568820, rs10735810, and rs731236 were genotyped using TaqMan assays. Results There were no differences among the caries risk groups in frequencies of the rs7975232, rs731236, rs1544410, or rs11568820 polymorphisms (χ2 test, P > 0.05); however, the frequency of the rs10735810 CC genotype was clearly higher in the high caries risk group than in the control and moderate caries risk groups (39.2%, 25.6%, and 30.6%, respectively; χ2 test, P=0.028). In multivariate analysis of genotypes and behavioral factors, rs7975232, rs731236, rs1544410, rs11568820, and rs10735810 were not associated with deciduous tooth decay (χ2 test, P > 0.05). Conclusion We conclude that these VDR polymorphisms cannot be used as markers for identification of Chinese children at increased risk of dental caries, when combined with environmental factors. Future studies are needed to replicate these initial findings and better assess the risk of caries in deciduous teeth.

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B - TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 - 18.297, p=0.024). IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

New approaches to pharmacogenetics of drug-induced hyperprolactinemia in patients with schizophrenia

The pathogenesis of the development of drug-induced disorders while taking antipsychotic drugs is not well understood. The aim of the work is to study polymorphic variants of the multidrug resistance protein gene and genes encoding the metabolism and synthesis of dopamine and serotonin enzymes in antipsychotic-induced hyperprolactinemia in schizophrenia patients. As a result of a comprehensive study of 446 patients with schizophrenia and genotyping of 25 polymorphic variants of the MDR1, COMT, MAO-A, MAO-B, TPH1 and TPH2 genes, associations of polymorphisms rs1045642, rs2032582, rs4148739 (MDR1), rs6323 (MAO-А), rs1799836 (MAO-B) were revealed with the development of hyperprolactinemia. Further research is needed to develop personalized approaches to therapy.

PNPLA3 and IL 28B signature for predicting susceptibility to chronic hepatitis C infection and fibrosis progression

Background Association studies identified genetic polymorphisms as predictive risk factors of rapid fibrosis progression in chronic hepatitis C (CHC). This study aims to assess the impact of IL28B rs8099917 polymorphism on CHC genotype 4 (G4) susceptibility and liver fibrosis progression individually; and in combination with PNPLA3 rs738409. Patients and methods IL28B rs8099917 and PNPLA3 rs738409 were genotyped in 150 Egyptian CHC patients and 175 healthy controls using real-time PCR. Results IL28B rs8099917 genotype distribution significantly differs in healthy individuals versus CHC patients (p = .018); and in low versus advanced fibrosis IL28B (p = .013). The haplotype CC –GG (PNPLA3-IL28B) is considered a high-risk signature for susceptibility to CHC infection. Similarly, GG–GG (PNPLA3-IL28B) is considered a high-risk signature for higher degree of fibrosis. Conclusion IL28B rs8099917 and PNPLA3 rs738409 introduce genetic signature to identify patients at higher risk for CHC susceptibility and fibrosis progression in CHC G4.

Single nucleotide polymorphisms rs12979860 and rs8099917 in IL-28B and spontaneous clearance of hepatitis C genotype 4

Hepatitis C virus (HCV) is associated with liver disease worldwide, an estimated 170 million are infected. The majority of the infected patients develop chronic liver disorders that range from fibr...

A functional polymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients.

Many genetic markers have been associated with variations in treatment response to analgesics, but none have been assessed in the context of combination therapies. In this study, the treatment effects of nortriptyline and morphine were tested for an association with genetic markers relevant to pain pathways. Treatment effects were determined for single and combination therapies. A total of 24 functional single nucleotide polymorphisms were tested within the gene loci of mu-opioid receptor (OPRM1) gene locus, ATP-Binding Cassette B1 Transporter (ABCB1), Cytochrome P450 gene family (CYP2C19 and CYP2D6), catecholamine inactivator Catechol-O-Methyl Transferase (COMT), and serotonin receptor 2A (HTR2A). Genotyping was performed in a population of neuropathic pain patients who previously participated in a clinical trial. For monotherapy, neither nortriptyline nor morphine responses were associated with single nucleotide polymorphisms. However, for nortriptyline + morphine combination therapy, the single nucleotide polymorphism rs1045642 within the drug efflux pump ABCB1 transporter significantly predicted analgesic response. The presence of the C allele accounted for 51% of pain variance in this subgroup in response to combination treatment. The T-allele homozygotes demonstrated only 20% improvement in pain scores, whereas the C-allele homozygotes 88%. There was no significant contribution of rs1045642 to the medication side effects under all treatment conditions. The UK Biobank data set was then used to validate this genetic association. Here, patients receiving similar combination therapy (opioid + tricyclic antidepressant) carrying the C allele of rs1045642 displayed 33% fewer body pain sites than patients without that allele, suggesting better pain control. In all, our results show a robust effect of the rs1045642 polymorphism in response to chronic pain treatment with a nortriptyline + morphine combination.

Association of IFNL3 rs12979860 polymorphism with HCV-related hepatocellular carcinoma susceptibility in a Chinese population.

BackgroundThe association between interferon lambda-3 (IFNL3，also known as interleukin 28B, IL28B) rs12979860 polymorphism and the development of hepatocellular carcinoma (HCC) has been investigated in recent studies with inconclusive and inconsistent results. IFNL3 rs12979860 polymorphism has been shown a marked differential distribution with regional and ethnic variation. Whether this single nucleotide polymorphism influences susceptibility to hepatitis C virus (HCV)-related HCC remains elusive.MethodsIn this case–control study, a total of 157 Chinese Han patients with chronic HCV infection were enrolled, including 62 HCV-related HCC patients and 95 chronic hepatitis C (CHC) patients without HCC, and the genetic polymorphism of IFNL3 rs12979860 was genotyped via a DNA microarray-based assay. The logistic regression analysis was employed to determine the correlation between the genetic polymorphism and risk of HCV-related HCC.ResultsA higher proportion of CT/TT genotype and T allele was observed in HCC patients compared to the CHC group. Under the genetic model of allele frequency, the T allele was associated with elevated risk of HCV-related HCC in the Chinese population compared to C allele after an adjustment for age, gender, body mass index, HCV infection duration, and HCV genotypes (P=0.046). In the subgroup analysis stratified by HCV genotype, subjects with CHC genotype 1b infection carrying rs12979860 T allele and CT+TT genotype had higher susceptibility to HCC than those with C allele and CC genotype (P=0.020, P=0.037, respectively).ConclusionIFNL3 rs12979860 polymorphism with T allele could be a factor that increases the risk of HCV-related HCC in the Chinese population, especially those subjects with CHC genotype 1b infection.

The association analysis between rs1544410 and rs10735810 polymorphisms located at VDR gene and susceptibility to Multiple Sclerosis in Iranian population

Multiple Sclerosis (MS) has been known to be one of the most common chronic inflammatory diseases with incidence almost 1 in 1000 individuals. Given that the vitamin D was involved in the regulation of immune response, the association of polymorphisms of this gene with MS risk has been reported in different Caucasian populations as well as Asians. In the present study, the association of two vitamin D receptor (VDR) polymorphisms including rs1544410 and rs10735810 with susceptibility to MS in Iranians was investigated. This study was performed on 118 MS patients and 120 healthy individuals. After extraction of genomic DNA from peripheral blood, the polymorphisms rs1544410 and rs10735810 were genotyped by PCR-RLFP. The results obtained from this study indicated that there was a significant association between rs1544410 and risk of affecting by MS in Iranians (OR = 1.96, 95% CI = 1.0–3.86, P = 0.047). In contrast, no association was observed between rs10735810 and MS susceptibility in the studied population (P > 0.05). These observations provided more understanding from the role of vitamin D metabolism in the pathogenesis of MS in Iranian population.

IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142–2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P < 0.0001). In conclusion, IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. These data highlight both common fibrosis pathways operating between organs, as well as differential effects within the same disease.

Interleukin 28B Polymorphism as a Predictor of Response to Treatment of Egyptian HCV Patients Working in Nuclear Material Authority

Background: A Single nucleotide polymorphism upstream of the interferon-λ3 gene (IFNL3; formerly referred to IL28B), strongly linked to unprompted and treatment-induced HCV infection clearance. Interleukin 28B genotype predictive value over the outcome interferon-α/ribavirin treatment was assessed carefully and contrasted with virological predictors Objective: The study aimed to evaluate IL-28B rs12979860 polymorphism in the reaction of HCV patients with directacting antiviral (DAA) regimens (sovosbuvir) and ribavirin therapy and the allele frequencies of this gene in Egyptian HCV patients working in the Egyptian Nuclear Materials Authority contrasted to healthy control. Subjects and Methods: The study was conducted on randomly chosen fifty Egyptian patients infected with genotype 4 HCV aged 30 or more and received antiviral therapy (sovosbuvir and ribavirin) before six months or more. Another Fifty age and gender matched apparantely healthy individuals were also selected as a control group. The study was carried out in accordance with the ethical principles and guidelines of the Declaration of Helsinki and a written informed consent was obtained from all subjects. Results:IL-28B genotype CC was found in 34.6% of patients, while CT and TT genotypes were identified in 42.3 and 23.1% of patients, respectively. Forty (40%) patients achieved an SVR, whereas ten (20%) did not. Of the 40 patients with an SVR, 12 had genotype CC, 25 had genotype CT, and 3 had genotype TT. CT genotype patients has achieved considerably higher SVR rates (62.5%) compared with CC (30%) and TT patients (7.5%). Conclusion: Polymorphism Il-28B is an autonomous predictor of SVR to Peg IFN / RBV in patients with genotype 4 in Egyptian HCV favorable.

Interleukin 28B Polymorphism as a Predictor of Response to Treatment of Egyptian HCV Patients Working in Nuclear Material Authority

Background: A Single nucleotide polymorphism upstream of the interferon-λ3 gene (IFNL3; formerly referred to IL28B), strongly linked to unprompted and treatment-induced HCV infection clearance. Interleukin 28B genotype predictive value over the outcome interferon-α/ribavirin treatment was assessed carefully and contrasted with virological predictors Objective: The study aimed to evaluate IL-28B rs12979860 polymorphism in the reaction of HCV patients with directacting antiviral (DAA) regimens (sovosbuvir) and ribavirin therapy and the allele frequencies of this gene in Egyptian HCV patients working in the Egyptian Nuclear Materials Authority contrasted to healthy control. Subjects and Methods: The study was conducted on randomly chosen fifty Egyptian patients infected with genotype 4 HCV aged 30 or more and received antiviral therapy (sovosbuvir and ribavirin) before six months or more. Another Fifty age and gender matched apparantely healthy individuals were also selected as a control group. The study was carried out in accordance with the ethical principles and guidelines of the Declaration of Helsinki and a written informed consent was obtained from all subjects. Results:IL-28B genotype CC was found in 34.6% of patients, while CT and TT genotypes were identified in 42.3 and 23.1% of patients, respectively. Forty (40%) patients achieved an SVR, whereas ten (20%) did not. Of the 40 patients with an SVR, 12 had genotype CC, 25 had genotype CT, and 3 had genotype TT. CT genotype patients has achieved considerably higher SVR rates (62.5%) compared with CC (30%) and TT patients (7.5%). Conclusion: Polymorphism Il-28B is an autonomous predictor of SVR to Peg IFN / RBV in patients with genotype 4 in Egyptian HCV favorable.

Connection between polymorphisms in HTR2A, TPH2, BDNF, TOMM40 genes and the successful mastering of human–computer interfaces

The development of human-computer interfaces in different individuals occur with different efficiencies, this is due to the individual characteristics of the genotype determined by the single-nucleotide polymorphism (SNP) of a person. Here, we checked the connection between the success of the acquisition of the brain-computer, eye-tracking, electromyographic, and respiratory interfaces and SNP of the TOMM40, BDNF, HTR2A and TPH2 genes. Here, we show that the T-allele in rs6313 of the HTR2A gene is associated with an increase in the number of correctly submitted commands of the electromyographic and eye-tracking interfaces. This is probably due to the fact that, the T-allele carriers decrease expression of this serotonin receptor. The decreased expression of HTR2A may be a reason for an increase in the number of accurately submitted commands. It was shown that the TT genotype of rs4290270 polymorphism was associated with an increase in the accuracy of work with the myographic interface. In addition, the association of subjective interfaces work time with polymorphisms rs429358 and rs2030324 was noted. Thus, the genotypic characteristics of individuals can be a predictive sign for the degree of success of mastering human-computer interfaces, which can allow to expand the understanding of training the neural mechanisms when working with this class of devices.

The MDR1/ABCB1 gene rs 1045642 polymorphism in colorectal cancer.

IntroductionColorectal cancer (CRC) is one of the most frequently diagnosed tumors in Western countries. CRC is a heterogeneous group of tumors with regards to its molecular pathogenesis and genetic factors. Both genetic variations and anthropometric factors may affect morbidity in CRC patients. The aim of this study was to assess the impact of multidrug resistance 1/ATP-binding cassette sub-family B member 1 gene (MDR1/ABCB1) polymorphism rs1045642 and general anthropometric factors on the CRC risk.Material and methodsThe study included 250 patients who underwent colonoscopy and polypectomy between 2006 and 2013 in a single endoscopy unit in Warsaw, Poland.ResultsThe CRC was diagnosed in 50 individuals, and 200 patients were included in the control group. Cases and controls were matched for mean age and sex (p > 0.05). Factors that were found to significantly increase the risk of CRC were ulcerative colitis (8/35 in the CRC group vs. 8/181 in the control group; p = 0.001), family history of CRC (11/33 vs. 26/172; p = 0.05), and diabetes mellitus (12/34 vs. 28/170; p = 0.04). Allele T of the rs 1045642 polymorphism was more frequently present in CRC cases (in both a co-dominant and recessive model) and in males (in a co-dominant model), although these associations were not statistically significant (p > 0.05).ConclusionsThe MDR1/ABCB1 gene polymorphism rs 1045642 may be involved in the pathogenesis of CRC and this relationship may be sex-specific for males. However, further population studies are necessary to assess this relationship.

IL28B Genetic Variations in Patients with Recurrent Herpes Simplex Keratitis.

Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype.

Association between Vascular Endothelial Growth Factor Plasma Levels and rs699947 Polymorphism and Coronary Collateral Vessel Formation

Background: The vascular endothelial growth factor (VEGF), as an angiogenic cytokine, binds endothelial cell receptors and stimulates angiogenesis and collateral formation. We evaluated the association between VEGF plasma levels and the gene polymorphism rs699947 and the formation of coronary collaterals in patients with coronary artery disease. Methods: A total of 195 patients with ≥70% narrowing in at least 1 coronary vessel (according to coronary angiography) were included in the study. The presence of the rs699947 polymorphism within the promoter of the VEGF gene was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma VEGF concentration was quantified via the ELISA method. The Rentrop method was used to grade the extent of collateral development. Results: There was no significant difference in VEGF levels between the groups with good and poor collaterals. The frequency of the A allele of rs699947 was found to be higher in the patients with good collaterals than in those with poor collaterals (P=0.014). The odds ratio of good collaterals for AA was 2.67 (P=0.025) when compared with the CC genotype. Further, our additive model revealed an association between the rs699947 polymorphism and collateral formation (OR: 1.96, 95% CI: 1.05-3.65, P=0.033). Conclusion: The rs699947 polymorphism might be a novel genetic factor affecting collateral development in Iranian patients with coronary artery disease.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta‐analysis

BackgroundThe present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC).MethodsA systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression‐free survival (PFS) and disease‐free survival (DFS) were collected and analysed.ResultsTwenty‐four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30–2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19–3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results.ConclusionsThe MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well‐designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

ABCG2 gene polymorphism rs2231142 is associated with gout comorbidities but not allopurinol response in primary gout patients of a Chinese Han male population

BackgroundOne common ATP-binding cassette subfamily G member 2 (ABCG2) gene variant, which is encoded by the single nucleotide polymorphism (SNP) rs2231142, was identified to take an essential part in gouty arthritis. However, the relationship between rs2231142, gout comorbidities and therapeutic effect of allopurinol in Chinese Han male population is still unclear. Wherefore, this study explored into the association between ABCG2 SNP rs2231142 affecting common comorbidities and the therapeutic effect of allopurinol in Chinese Han male gout patients.ResultsABCG2 SNP rs2231142 and the gout comorbidities including nephrolithiasis and CKD were associated (P = 0.014 and P = 0.026). Group CKD stage = 1 were significantly different from those in group CKD stage≥2 regarding genotypes of ABCG2 gene polymorphism, while they were not significantly different from those in group CKD stage≥3. Meanwhile, the genotypes of rs2231142 and allopurinol response were not significantly associated (P = 0.588).ConclusionsABCG2 rs2231142 may predict the risk of kidney comorbidities for Chinese Han male gout patients, but not allopurinol response.