Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution

BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables

Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.

Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.

Updating Genetics Polymorphisms of Non-Syndromic Clefts Lip-Palates

Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.

Genetic Polymorphism of Eighteen Lycium barbarum Resources Based on nrDNA ITS Sequence

[Objective] The study aimed to investigate the genetic polymorphism of eighteen Lycium barbarum resources via nrDNA ITS sequencing. [Method] The genomic DNAs from Lycium barbarum leaves were isolated by modified CTAB method for PCR amplification on the nrDNA ITS region using specifically synthesized primers; the amplified fragments were cloned and sequenced, then the sequencing results were clustered. [Result] nrDNA ITS sequences of the tested eighteen Lycium barbarum were firstly obtained in the present study. For all eighteen tested materials, the variation range of whole ITS region was 559-634 bp, with an average of 612 bp; alignment analyses showed that the whole length of internal transcribed spacer (ITS1+ITS2) was 480 bp, within which there are 194 variation sites (accounting for 40.4%) and 286 conserved sites (accounting for 59.6%). The cluster results showed that the eighteen tested materials could be grouped into three classes. [Conclusion] Analysis of nrDNA ITS sequence may avail to identify the Lycium barbarum germplasm resources.

Characterization of Genetic Polymorphism of Novel MHC B-LBⅡ Alleles in Chinese Indigenous Chickens

Genetic polymorphism of the major histocompatibility complex （MHC） B-LBⅡ gene was studied by amplification of exon 2 using PCR, followed by cloning and DNA sequencing in eight indigenous Chinese chicken populations. To reveal the genetic variation of the B-LB Ⅱ gene, 37 types of patterns detected by PCR-SSCP were investigated first, which would be used to screen novel B-LB Ⅱsequences within the breeds. The types of PCR-SSCP patterns and final sequencing allowed for the identification of 31 novel MHC B-LBⅡ alleles from 30 unrelated individuals of Chinese chickens that were sampled. These are the first designators for the alleles of chicken MHC B-LBⅡ gene based on the rule of assignment for novel mammalian alleles. Sequence alignment of the 31 B-LB Ⅱ alleles revealed a total of 68 variable sites in the fragment of exon 2, of which 51 parsimony informative and 17 singleton variable sites were observed. Among the polymorphic sites, the nucleotide substitutions in the first and second positions of the codons accounted for 36.76% and 35.29%, respectively. The sequence similarities between the alleles were estimated to be 90.6%-99.5%. The relative frequencies of synonymous and nonsynonymous nucleotide substitutions within the region were 2.92%±0.94% and 14.64%±2.67%, respectively. These results indicated that the genetic variation within exon 2 appeared to have largely arisen by gene recombination and balancing selection. Alignment of the deduced amino acid sequences of the β1 domain coded by exon 2 revealed 6 synonymous mutations and 27 nonsynonymous substitutions at the 33 disparate sites. In particular, the nonsynonymous substitutions at the putative peptide-binding sites are considered to be associated with immunological specificity of MHC B-LB Ⅱ molecule in Chinese native chickens. These results can provide a molecular biological basis for the study of disease resistance in chicken breeding.

Genetic Polymorphism of Wheat by IRAP Analysis Based on Retrotransposon Wis2-1 A

[Objective] To analyze genetic polymorphism of different species of wheat. [Method] The DNA of young seedlings from 21 species of wheat was isolated,and their genetic polymorphism was analyzed by inter-retrotransposon amplified polymorphism （IRAP） using a molecule marker technology based on wheat retrotransposon Wis2-1 A. [Result] As shown by clustering map of the electrophoresis results,19 species of wheat assembled as cluster with different genetic distance. Most of the wheat species were distinguished. The genetic polymorphism among different species of wheat could be evaluated by this method objectively. [Conclusion] The analysis of IRAP based on wheat retrotransposon Wis2-1A could give a basis for breeding of wheat.

A Novel Genetic Polymorphism and Its Genetic Effects of Porcine Heart Fatty Acid-Binding(H-FABP)Gene in Intron 1

[Objective] The aim was to provide basic reference for the use of H-FABP gene in marker-assisted selection of the breeding process of pig.[Method] Single-nucleotide polymorphisms of the H-FABP gene in Shanxi White pig,Mashen pig,Large White pig,Landrace and Duroc were tested by PCR-SSCP,and the correlation between genotype and intramuscular fat content in pigs were analyzed.[Result] One polymorphism was found in the amplified region of intron 1 of porcine H-FABP gene,in which two alleles（A and B）and three genotypes（AA,AB,and BB）were examined.C→T transition was detected by sequencing the homozygotes.The multiple comparison of the distribution of genotype in different pig varieties revealed that Mashen pig showed extremely significant difference（P0.01）in genotype distribution with Shanxi White,Landrace,Large White and Duroc breeds;whereas no significant differences（P0.05）were found in genotype distribution between other breeds.Based on the fixed effect model,extremely significant differences（P 0.01）were found in the intramuscular fat content among different H-FABP genotypes.Using least square analysis,it was found that there was significant differences（P 0.05）in the intramuscular fat content between the individuals of the BB genotypes and those of the AA genotypes.[Conclusion] The H-FABP genotype had significant effects on the meat quality.

Genetic Polymorphism of Ten Microsatellites in Two Goat Breeds and Its Relationship with Heterosis

[Objective] This study aimed to investigate the genetic diversity of Macheng black goat and its correlation with heterosis.[Method] Ten microsatellite markers were selected for polymorphism investigation and statistical analysis of Boer goat and Macheng black goat populations.[Result] The results showed that totally 175 alleles were found in 10 microsatellite loci; to be specific,the maximum number of detected alleles was 23,and the minimum number was 10; the effective number of alleles （Ne） was 6.4-18.1,with absolute difference value of 1.6-8.1 from the observed number of alleles.The highest gene frequency was 0.239 1 and the lowest was 0.002 7.The polymorphic information contents of all the ten microsatellite markers were above 0.95.The observed heterozygosity （Ho） ranged from 0.616 7 to 0.984 4 and the expected heterozygosity （He） ranged from 0.844 1 to 0.944 6.The average expected heterozygosity of Boer goat and Macheng black goat was respectively 0.894 0 and 0.906 7.Various body weight and body size indices of Boer goatxMacheng black goat hybrids were improved in varying degrees compared with Macheng black goat （with an increase range of 0.32％-30.06％）.The average heterosis rates of body height and chest girth were relatively high,while average heterosis rate of body weight was relatively low.[Conclusion] The genetic distance between Boer goat and Macheng black goat was 0.379 5,which is consistent with the geographical distribution of Boer goat and Macheng black goat populations and is fully relevant to the heterosis of Boer goat × Macheng black goat hybrids,indicating that investigating polymorphism via microsatellite loci is one of the feasible means to predict and analyze heterosis between varieties.

Genetic Polymorphism of Mitochondrial DNA in Dong,Gelao,Tujia,and Yi Ethnic Populations from Guizhou,China

To reveal the genetic structures and relationships of the four ethnic populations from the maternal inheritance and explore the origins and migrations of nationalities, the genetic polymorphism of mtDNA in Dong, Gelao, Tujia, and Yi populations from Guizhou was studied by direct sequencing of hypervariable segment Ⅰ （HVS Ⅰ ） and PCR-RFLP of coding region. Thirty-seven （sub-） haplogroups were identified in the classification tree of mtDNA haplogroups. Haplogroup distributions and principal component （PC） analysis showed that the Dong has high frequencies of south-prevalent haplogroups, which indicates that it is a typically southern population. The Yi harbors high frequencies of the south-prevalent and northern-prevalent haplogroups, which demonstrates that it inherits the maternal characteristics from both southern and northern populations. The Yi and Gelao cluster together, the reason for which might be that their ancestries frequently underwent gene exchanges and mixtures.

The Relationship between Genetic Polymorphisms of Three Gene Loci and Growth Characters of Haimen Goats

[Objective] The paper aims to study the relationship between genetic polymorphisms of three gene loci and growth character of Haimen Goats to provide reference to promote Haimen Goat growth character and cultivate Haimen Goat new strain of fast-growth.[Method] We processed analysis and related statistical analysis on three gene loci of Haimen Goats with PCR-RFLP and PCR-SSCP.[Result] The results suggested that there were two genotypes in MSTN gene IntronⅡ,GH gene exonⅠ and GH gene exonⅡ in Haimen Goats.Different genotypes of these gene loci had different effects on relative growth character of Haimen Goats.[Conclusion] This study had a significant meaning about promoting Haimen Goat avoirdupois by marker assistant option.

Studies on Genetic Polymorphism of Different Biotypeswith RAPD Analysis1

In the present paper, RAPD was used to study the genetic polymorphism of fisheswith different genome combinations. Our results indicated that four of the 26 random primersproduced distinct and reproducible electrophoretic patterns which were genome-specific andcould distinguish different biotypes. This enabled us to derive a diagnostic profile, from whichwe constructed a molecular marker key for different biotypes. By the analysis of the data ofRAPD patterns, the genetic relationship was constructed with UPGMA (unweighted pair-groupmethod with arithmetical averages). Our experiments also concluded that RAPD was moresuccessful in variety identification than protein polymorphism analysis and serohematology for itstechnological simplicity and sensitivity.

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

Glutathione S-transferases （GSTs）, superoxide dismutase 2 （SOD2） and NAD（P）H：quinone oxidoreductase 1 （NQO1） are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase 7：1 （GSTT1）-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction （PCR）. Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism （PCR-RFLP） method. A significantly better response to varicocelectomy was found in patients with the GSTTI-wt genotype （63.2%） and NQO1-Ser/Ser genotype （80.0%） than in those with GSTTI-null genotype （35.3%） and NQO1-Pro/Pro or NQO1- Pro/Ser genotype （45.2%）, respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China

Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）

Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China

AIM＂ TO evaluate the impact of alcohol dehydrogenase 2 （ADH2） and aldehyde dehydrogenase 2 （ALDH2） polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer （PCR-CTPP） method. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （95% CI）. RESULTS; Both ADH2＊1 allele and ALDH2＊1/＊2 allele showed an increased risk of developing esophageal cancer. The adjusted OR （95% CI） for ADH2＊1 allele compared with ADH2＊2/＊2 was 1.65 （95% CI = 1.02-2.68） and 1.67 （95% CI = 1.02-2.72） for ALDH2＊1/＊2 compared with ALDH2＊1/＊1. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83 （95% CI = 1.13-2.95）. Furthermore, when compared with ADH2＊2/＊2 and ALDH2＊1/＊1 carriers, ADH2＊1 and ALDH2＊2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers

Genetic polymorphisms in HIFIA are associated with prostate cancer risk in a Chinese population

The hypoxia-inducible factor-1α（HIF-1α） plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIFIA （coding HIF-1α） have been shown to influence an individual＇s susceptibility to many human tumors; however, evidence on associations between HIFIA single-nucleotide polymorphisms （SNPs） and prostate cancer （PCa） risk is conflicting. We genotyped three potentially functional polymorphisms in HIFIA （rs11549465, rs11549467 and rs2057482） using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Hart population. Compared with rs 11549467 GG genotype, the variant genotypes GA ＋AA had a significantly increased PCa risk （adjusted odds ratio （OR）= 1.70; 95% confidence interval （C1）= 1.06-2.72）, particularly among older patients （0R=2.01; 95%C1 = 1.05-3.86）, smokers （0R=2.06; 95%C1 = 1.07-3.99）, never drinkers （OR=2.16; 95%C1 = 1.20-3.86） and patients without a family history of cancer （OR= 1.71; 95%C1= 1.02-2.89）. Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score （OR=2.14; 95%CI = 1.22-3.75）. No altered PCa risk was associated with the rs 11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs 11549467 were associated with increased PCa risk （0R=2.10; 95%C1= 1.23-3.57 among subjects carrying three or more risk alleles）. These results suggest that HIFIA polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.

Genetic polymorphism in pathogenesis of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a complex symptom-based disorder without established biomarkers or putative pathophysiology. IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3 mo according to ROME III: relief by defecation, onset associated with a change in stool frequency or onset with change in appearance or form of stool. Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms, as well as the therapeutic responses in treating IBS patients. This review gives new insights on how genetic determinations influence in clinical manifestations, treatment responses and potential biomarkers of IBS.

Genetic polymorphism and mRNA levels of cytochrome P450ⅡE1 and glutathione S-transferase P1 in patients with alcoholic liver disease in different nationalities

BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in northeast China.This study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes,cytochrome P450ⅡE1(CYPⅡE1)and glutathione S-transferase P1(GSTP1)in patients of three nationalities.METHODS:Peripheral blood was collected from 353 Chinese patients with ALD,300 alcohol dependent patients without liver disease(alcoholic),and 360 healthy controls.Each group included patients from the Han,Mongol and Korean nationalities.Real-time polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP)were used.RESULTS:Regardless of nationality,patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of ALD.The frequency of C2 and Val in patients with ALD was respectively 50.00%and 26.98%in the Han,31.36%and 22.87%in the Mongol,and 45.87%and 22.02% in the Korean nationality.No significant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three nationalities.In each nationality,the frequency of both C2 and Val alleles was significantly higher in ALD compared to alcoholic and healthy controls.Except for nationality,the average mRNA levels of CYPⅡ E1 in ALD patients and healthy controls were 10.05%and 2.21%,respectively.The average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53%and 2.12%,respectively.The mRNA level of CYPⅡE1 was higher,and that of GSTP1 was lower in patients with ALD compared to the controls.CONCLUSIONS:Except for nationality,patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele,and tended to have a lower mRNA expression of GSTP1 and to carry the Val allele.There is a causal relationship between the polymorphic alleles,which leads to different mRNA levels and the development of ALD.