OPRM1(A118G)基因多态性与肺癌癌痛患者镇痛效果的相关性

目的:探讨阿片样物质受体(μ1 opioid receptor,OPRM1)(A118G)基因多态性与肺癌癌痛患者镇痛效果的相关性。方法:选取本院2017年3月至2019年10月收治的360例肺癌患者作为研究对象,判断患者阿片耐受与不良反应发生情况。收集患者血液指标,检测OPRM1(A118G)基因多态性情况并进行相关性分析。结果:在360例患者中,阿片耐受78例(耐受组),耐受率为21.7%;耐受组的性别、年龄、体重指数、肿瘤最大直径等与非耐受组对比差异无统计学意义(P0.05),两组临床分期与淋巴结转移等对比差异有统计学意义(P0.05)。OPRM1(A118G)基因共有AA、AG、GG三种基因型,两组人群的OPRM1(A118G)基因型分布均符合Hardy-Weinberg平衡定律;两组OPRM1(A118G)基因型分布差异具有统计学意义,耐受组的OPRM1(A118G)基因GG基因型比例显著高于非耐受组(P0.05),等位基因G频率显著高于非耐受组(P0.05);耐受组的呼吸抑制、恶心呕吐、头晕、皮肤瘙痒等不良反应发生率为35.9%,显著高于非耐受组的2.8%(P0.05)。直线相关性分析显示OPRM1(A118G)基因GG基因型与阿片耐受、淋巴结转移、临床分期都呈现相关性(P0.05);二分类变量Logistic回归分析显示OPRM1(A118G)基因GG基因型、临床分期、淋巴结转移为影响阿片耐受的主要因素(P0.05)。结论:肺癌癌痛患者在镇痛中存在阿片耐受情况,与患者的OPRM1(A118G)基因多态性与治疗不良反应显著相关,OPRM1(A118G)基因GG基因型、临床分期、淋巴结转移为影响阿片耐受的主要因素。     

Functional polymorphism of the mu-opioid receptor gene (OPRM1) influences reinforcement learning in humans

Previous reports on the functional effects (i.e., gain or loss of function), and phenotypic outcomes (e.g., changes in addiction vulnerability and stress response) of a commonly occurring functional single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine the effect of this polymorphism on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy adult subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response--that is, their bias to the rewarded stimulus increased over time. However, OPRM1 G allele carriers exhibited a decline in response to the rewarded stimulus compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. Through comparison with other studies using this task, we suggest a possible mechanism by which the OPRM1 polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning.     

Polymorphism G861C of 5-HT receptor subtype 1B is associated with heroin dependence in Han Chinese

The serotoninergic (5-HT) system regulates neuronal activity in broad brain regions, and appears to be particularly important for modulating behavioral and physiological functions such as mood, emotion, sleep and appetite. Central 5-HT deregulation may be involved in many neuropsychological disorders, which include substance abuse and addiction. Previous studies suggest that genetic polymorphisms in some 5-HT receptor genes may relate to heroin dependency. Here we examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of 5-HT receptors (A-1438G and T102C of HTR_2A, and G861C and A1180G of HTR_1B) in a cohort of Han Chinese. Participants included 303 heroin-dependent subjects who were recruited into the Methadone Maintenance Treatment (MMT) Program in the Xi’an Mental Health Center, and 300 healthy controls. The resulting data yielded a significantly higher frequency of the HTR_1B G allele with G861C among the heroin-dependent subjects relative to controls (p = 0.001 after Bonferroni correction). Further genotype and clinical phenotype correlation study of the G861C carriers showed that the amount of heroin self-injection was higher in patients with the GG genotype relative to CC and CG genotypes (p < 0.01). These findings point to a role for HTR_1B polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.     

OPRM1 Gene Is Associated With BMI in Uyghur Population

To test the hypothesis that µ‐opioid receptor (OPRM1) gene might be involved in the prevalence of obesity, a population‐based association study was carried out in Uyghur population. Overall 10 tagging single‐nucleotide polymorphisms (tSNPs) in OPRM1 gene were genotyped. We showed that genotypes of rs1799971 in exon 1, and rs514980 and rs7773995 in intron 1 were significantly associated with the BMI. The BMI significantly decreased by the copy of minor allele carriers of rs1799971 which is a nonsynonymous functional polymorphism, whereas the BMI significantly increased by the copy of minor allele carriers of rs514980 and rs7773995. Subsequently, subjects were subsequently divided into case (BMI ≥ 28) and control group (BMI < 24). Significant associations were again observed at rs1799971, rs514980, and rs7773995, regardless of controlling for covariates age and gender or not. The stronger evidence for association was found under the additive model for each of the three SNPs. The per‐allele odds ratio of the minor allele for obesity was 0.75 (95% confidence interval 0.58–0.96, P = 0.023) for rs1799971, 1.68 (95% confidence interval 1.14–2.49, P = 0.009) for rs514980, and 1.80 (95% confidence interval 1.14–2.85, P = 0.012) for rs7773995, respectively. Our observations give the evidence that OPRM1 gene is involved in the prevalence of obesity in Uyghurs.     

Dopamine for “Wanting” and Opioids for “Liking”: A Comparison of Obese Adults With and Without Binge Eating

Obesity research suffers from an overinclusion paradigm whereby all participants with a BMI beyond a certain cutoff value (e.g., 30) are typically combined in a single group and compared to those of normal weight. There has been little attempt to identify meaningful subgroups defined by their salient biobehavioral differences. In order to address this limitation, we examined genetic and psychological indicators of hedonic eating in obese adults with (n = 66) and without (n = 70) binge eating disorder (BED). Our analyses focused on dopamine (DA) and opioid genetic markers because of their conjoint association with the functioning of brain reward mechanisms. We targeted three functional polymorphisms related to the D2 receptor (DRD2) gene, as well as the functional A118G polymorphism of the mu‐opioid receptor (OPRM1) gene. We found that significantly more obese controls had the “loss‐of‐function” A1 allele of Taq1A compared to their BED counterparts, whereas the “gain‐of‐function” G allele of A118G occurred with greater frequency in the BED group. A significant gene–gene combination χ² analysis also indicated that of those participants with the gain‐gain genotype (G⁺ and A1), 80% were in the BED group whereas only 35% with the loss‐loss genotype (G^? and A1⁺) were in this group. Finally, BED subjects had significantly higher scores on a self‐report measure of hedonic eating. Our findings suggest that BED is a biologically based subtype of obesity and that the proneness to binge eating may be influenced by a hyper‐reactivity to the hedonic properties of food—a predisposition that is easily exploited in our current environment with its highly visible and easily accessible surfeit of sweet and fatty foods.     

A common single nucleotide polymorphism A118G of the μ opioid receptor alters its N-glycosylation and protein stability

The A118G SNP (single nucleotide polymorphism) of the hMOPR [human MOPR (μ opioid receptor)] gene OPRM1 results in an amino acid substitution (N40D). Subjects homozygous for the 118G allele have been reported to require higher morphine doses to achieve adequate analgesia, and the 118G allele is more prevalent among drug abusers. However, changes in the MOPR protein associated with this SNP are unknown. Using a knockin mouse model (G/G mice; mice homozygous for the 112G allele of MOPR) that possesses the equivalent nucleotide/amino acid substitution (A112G; N38D) of the A118G SNP in the hMOPR gene, we investigated the N-linked glycosylation status of thalamic and striatal MOPR in G/G mice compared with A/A mice (wild-type mice homozygous for the 112A allele of MOPR). The molecular mass of MOPR determined by immunoblotting was lower in G/G mice than in A/A mice. Following treatment with peptide N-glycosidase F, which removes all N-linked glycans, both MOPR variants had an identical molecular mass, indicating that this discrepancy was due to a lower level of N-glycosylation of the MOPR in G/G mice. In Chinese-hamster ovary cells stably expressing hMOPRs, 118G/Asp40-hMOPR had a lower molecular mass than 118A/Asn40-hMOPR, which was similarly due to differential N-glycosylation. Pulse-chase studies revealed that the half-life of the mature form of 118G/Asp40-hMOPR (~12?h) was shorter than that of 118A/Asn40-hMOPR (~28?h). Thus the A118G SNP reduces MOPR N-glycosylation and protein stability.     

Association of µ-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis

Previous studies have suggested that the effect of naltrexone in patients with alcohol dependence may be moderated by genetic factors. In particular, the possession of the G allele of the A118G polymorphism of the μ-opioid receptor gene (OPRM1) has been associated with a better response to naltrexone, although controversial results have been reported. The aim of this paper is to combine previous findings by means of a systematic review and a meta-analysis. We retrieved studies on the relationship between A118G polymorphism in OPRM1 gene and response to treatment with naltrexone in patients with alcohol dependence by means of electronic database search. A meta-analysis was conducted using a random-effects model. Calculations of odds ratio (OR) and their confidence intervals (CI) and tests for heterogeneity of the results have been performed. Six previous studies have analyzed the role of A118G polymorphism in response to naltrexone for alcohol dependence. After meta-analysis, we found that naltrexone-treated patients carrying the G allele had lower relapse rates than those who were homozygous for the A allele (OR: 2.02, 95% CI 1.26-3.22; P = 0.003). There were no differences in abstinence rates. Our results support the fact that the G allele of A118G polymorphism of OPRM1 moderates the effect of naltrexone in patients with alcohol dependence. This genetic marker may therefore identify a subgroup of individuals more likely to respond to this treatment.     

Functional polymorphism of the MMP-1 promoter (-1607 1G/2G) in potentially malignant and malignant head and neck lesions in an Indian population

Matrix metalloproteinases (MMP) are a family of zinc-dependent proteases that degrade the entire component of the extracellular matrix. Our study explores the association of the MMP1 gene promoter (-1607 1G/2G) polymorphisms in oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) in an Indian population. The MMP1single-nucleotide polymorphism (SNP) was genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 412 patients with OSMF, 422 with HNSCC and 426 controls. Our results showed that the frequency of 1G/2G or 2G/2G promoter genotypes having the 2G allele is associated with higher enzymatic activity and significantly increases in OSMF (p<0.001) and HNSCC cases (p<0.00). In this study, results concluded that SNPs in the MMP1 promoter region may be associated with susceptibility to OSMF as well as HNSCC in an Indian population and addiction habits such as areca nut chewing and alcohol abuse may enhance the expression of the 2G allele of MMP1 genes in OSMF and HNSCC cases.     

Epigenetic variation in OPRM1 gene in opioid‐exposed mother‐infant dyads

Neonatal abstinence syndrome (NAS) due to in‐utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ‐opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid‐exposed mother‐infant dyads is associated with differences in NAS severity in an independent cohort. Full‐term opioid‐exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next‐generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the ?18 (11.4% vs 4.4%, P = .0001), ?14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the ?169 (R = 0.43, P = .008), ?152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point‐wise with longer infant length of stay. Maternal associations remained significant point‐wise for ?169 (β = 0.07, P = .007) and on an experiment‐wise level for +84 (β = ?0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.     

Do genetic predictors of pain sensitivity associate with persistent widespread pain?

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and μ opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at ≥2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the χ² test. Allele frequencies and carriage of the minor allele was compared between cases and controls using χ² tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP.     

Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms

Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America.     

The genetic influence on the cortical processing of experimental pain and the moderating effect of pain status

Background

Research suggests that the COMT Val¹⁵⁸Met, BDNF Val⁶⁶Met and OPRM1 A¹¹⁸G polymorphisms moderate the experience of pain. In order to obtain experimental confirmation and extension of findings, cortical processing of experimentally-induced pain was used.

Method

A sample of 78 individuals with chronic low back pain complaints and 37 healthy controls underwent EEG registration. Event-Related Potentials were measured in response to electrical nociceptive stimuli and moderation by COMT Val¹⁵⁸Met, BDNF Val⁶⁶Met and OPRM1 A¹¹⁸G polymorphisms was assessed.

Results

Genetic variation did not have a direct effect on cortical processing of experimental pain. However, genetic effects (COMT Val¹⁵⁸Met and BDNF Val⁶⁶Met) on experimental pain were moderated by the presence of chronic pain. In the presence of chronic pain, the COMT Met allele and the BDNF Met allele augmented cortical pain processing, whilst reducing pain processing in pain-free controls. No significant effects were found concerning the OPRM1 A¹¹⁸G polymorphism.

Conclusions

The current study suggests that chronic experience of pain enhances genetic sensitivity to experimentally induced mildly painful stimuli, possibly through a process of epigenetic modification.     

Opioid Exposure is Associated with Aberrant DNA Methylation of <Emphasis Type="Italic">OPRM1</Emphasis> Promoter Region in a Chinese Han Population

The μ-opioid receptor (OPRM1) plays an important role in opiate addiction. The OPRM1 gene promoter showed hypermethylation in lymphocytes of opiate addicts as well as opioid medications users, while the methylation status displayed ethnic diversity. The purpose of the study was to investigate the methylation pattern of OPRM1 promoter in the Han Chinese population. We analyzed 22 CpG sites located in OPRM1 promoter in 186 former opiate addicts (94 males and 92 females) and 184 healthy controls (102 males and 82 females). The +?126 CpG site was significantly hypermethylated in the former heroin addicts compared with controls (13.67% versus 8.39%, \(P = 3.78 \times 10^{ - 9}\), corrected for 36 tests). Six CpG sites were significantly associated with opioid exposure, including the most significant +126 CpG site (opiate addicts 13.57%, control 8.39%, \(P = 9.19 \times 10^{ - 12}\), corrected for 36 tests), while the +23 GpG site was the only hypomethylated one in former opiate addicts compared with controls (P?=?0.0023 after Bonferroni correction). Our results supported that opioid exposure was associated with methylation status of OPRM1 promoter and showed ethnic dependence.     

SLC6A4基因多态性与海洛因依赖的关联性研究

目的:探讨5-羟色胺转运体基因(solute carrier family 6 member 4,SLC6A4)基因4个单核苷酸多态性(single nucleotide polymorphism,SNP)位点与海洛因依赖之间的关系。方法:严格按照诊断标准,选取无亲缘关系的海洛因依赖个体397例(病例组)及健康对照个体402例(对照组)提取基因组DNA,采用SNaPshot SNP分型技术对SLC6A4基因4个SNP位点(rs1042173,rs3813034,rs6354,rs7224199)进行基因分型,比较病例-对照组间各位点等位基因、基因型频率的差异。结果:病例组和对照组SLC6A4基因rs1042173和rs3813034位点的基因型和等位基因频率比较存在显著性差异(P0.05),rs1042173的C等位基因(P=0.031,OR=1.317,95%CI=1.026-1.691)及rs3813034的C等位基因(P=0.013,OR=1.375,95%CI=1.069-1.768)是海洛因依赖的危险因素。病例组TCC单倍型(rs7224199、rs3813034和rs1042173)的比例较对照组显著增高(P0.05)。结论:SLC6A4基因rs1042173和rs3813034多态性可能与海洛因成瘾有关,携带有rs1042173的C等位基因和rs3813034的C等位基因的个体及携带TCC单倍型的个体可能更容易对海洛因产生依赖。     

Cytochrome P450 1A1 gene polymorphisms and digestive tract cancer susceptibility: a meta‐analysis

Cytochrome P450 1A1 (CYP1A1) is a phase I enzyme that regulates the metabolism of environmental carcinogens and alter the susceptibility to various cancers. Many studies have investigated the association between the CYP1A1 MspI and Ile462Val polymorphisms and digestive tract cancer (DTC) risk in different groups of populations, but their results were inconsistent. The PubMed and Embase Database were searched for case–control studies published up to 30th September, 2015. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the relationship. Totally, 39 case–control studies (9094 cases and 12,487 controls) were included. The G allele in Ile/Val polymorphism was significantly associated with elevated DTC risk with per‐allele OR of 1.24 (95% CI = 1.09–1.41, P = 0.001). Similar results were also detected under the other genetic models. Evidence was only found to support an association between MspI polymorphism and DTC in the subgroups of caucasian and mixed individuals, but not in the whole population (the dominant model: OR = 1.19, 95% CI = 0.94–1.91, P = 0.146). In conclusion, our results suggest that the CYP1A1 polymorphisms are potential risk factors for DTC. And large sample size and well‐designed studies with detailed clinical information are needed to more precisely evaluate our founding.     

Gender Interacts with Opioid Receptor Polymorphism A118G and Serotonin Receptor Polymorphism −1438 A/G on Speed-Dating Success

We examined an understudied but potentially important source of romantic attraction—genetics—using a speed-dating paradigm. The mu opioid receptor (OPRM1) polymorphism A118G (rs1799971) and the serotonin receptor (HTR2A) polymorphism ?1438 A/G (rs6311) were studied because they have been implicated in social affiliation. Guided by the social role theory of mate selection and prior genetic evidence, we examined these polymorphisms’ gender-specific associations with speed-dating success (i.e., date offers, mate desirability). A total of 262 single Asian Americans went on speed-dates with members of the opposite gender and completed interaction questionnaires about their partners. Consistent with our prediction, significant gender-by-genotype interactions were found for speed-dating success. Specifically, the minor variant of A118G (G-allele), which has been linked to submissiveness/social sensitivity, predicted greater speed-dating success for women, whereas the minor variant of ?1438 A/G (G-allele), which has been linked to leadership/social dominance, predicted greater speed-dating success for men. For both polymorphisms, reverse “dampening” effects of minor variants were found for opposite-gender counterparts. These results support previous research on the importance of the opioid and serotonergic systems in social affiliation, indicating that their influence extends to dating success, with opposite, yet gender-norm consistent, effects for men and women.     

CYP1A1 rs1048943 and rs4646903 polymorphisms associated with laryngeal cancer susceptibility among Asian populations: a meta‐analysis

Many studies have investigated the association between CYP1A1 rs1048943 and rs4646903 polymorphisms and laryngeal cancer risk, but their results have been inconsistent. The PubMed and CNKI were searched for case–control studies published up to 01 July 2015. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta‐analysis, we assessed 10 published studies involving comprising 748 laryngeal cancer cases and 1558 controls of the association between CYP1A1 rs1048943 and rs4646903 polymorphisms and laryngeal cancer risk. For CYP1A1 rs1048943 of the homozygote G/G and G allele carriers (A/G + G/G) versus A/A, the pooled ORs were 1.77 (95% CI = 1.28–2.81, P = 0.007 for heterogeneity) and 1.86 (95% CI = 1.45–2.40, P = 0.000 for heterogeneity). For CYP1A1 rs4646903 of the homozygote G/G and G allele carriers (A/G + G/G) versus A/A, the pooled ORs were 1.53 (95% CI = 1.31–2.21, P = 0.012 for heterogeneity) and 1.33(95% CI = 1.04–1.71, P = 0.029 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians for both the G allele carriers and homozygote G/G. However, no significant associations were found in Caucasian population all genetic models. These results from the meta‐analysis suggest that CYP1A1 rs1048943 and rs4646903 polymorphisms contribute to risk of laryngeal cancer among Asian populations.     

ICAM‐1 and MKL‐1 polymorphisms impose considerable impacts on coronary heart disease occurrence

This study was aimed to explore the correlation of intercellular adhesion molecule‐1 (ICAM‐1) K469E and megakaryoblastic leukaemia factor‐1 (MKL‐1) ?184C/T polymorphisms with the susceptibility to coronary heart disease (CHD) in the Chinese Han population. 100 CHD patients and 91 healthy people that had no blood connection with each other were enrolled in this case‐control study. ICAM‐1 and MKL‐1 polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) approach. Multiple logistic regression was used to analyse the correlation between polymorphisms of ICAM‐1 and MKL‐1 and CHD susceptibility. Differences of genotype and allele frequencies of the two SNPs between case and control groups were analysed by chi‐square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were indicated relative susceptibility of CHD. The distributions of ICAM‐1 and MKL‐1 polymorphisms in each group conformed to Hardy‐Weinberg equilibrium (HWE). After adjusting for traditional risk factors, the TT genotype frequency of MKL‐1 ?184C/T polymorphism was found significantly higher in case group than in control group (P < .05). Meanwhile, T allele frequency increased in case group compared with control group, and the differences had statistical significance (P = .04, OR = 2.34, 95% CI = 1.34‐5.26). Logistic regression analysis in this study proved that smoking, hypertension, diabetes and triglyceride (TG) were all risk factors for CHD ICAM‐1 K469E polymorphism has no association with the onset of CHD. But MKL‐1 ?184C/T polymorphism is associated with the risk of CHD and T allele might be a susceptibility factor for CHD.     

Polymorphic variants of folate metabolizing genes (C677T and A1298C <Emphasis Type="Italic">MTHFR</Emphasis> and C1420T SHMT1 and G1958A <Emphasis Type="Italic">MTHFD</Emphasis>) are not associated with the risk of breast cancer in the West Siberian Region of Russia

Breast cancer is one of the most widely distributed cancers in women. We investigated the role of allele variants in the folate metabolizing genes MTHFR (C677T and A1298C alleles), SHMT1 (C1420T allele), and MTHFD (G1258A allele) as a possible factor in predisposition to breast cancer. We determined allele and genotype frequencies of single nucleotide polymorphisms (SNPs) in the case (850 women with sporadic form of breast cancer) and control (810 healthy women) groups. None of the polymorphisms were significantly associated with breast cancer risk. To increase the statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. The meta-analysis revealed no significant association between the studied SNPs and breast cancer risks either.