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.

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.

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.

Relationship between the acid-suppression efficacy of proton pump inhibitors and CYP2C19 genetic polymorphism in patients with peptic ulcer

Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.

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.

Ethnic differences in genetic polymorphism associated with irritable bowel syndrome

Genetic polymorphism is associated with irritable bowel syndrome(IBS)in terms of susceptibility and clinical manifestations.Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis,gastrointestinal motility,inflammatory activity,and immune status.Although underlying pathophysiological mechanisms have not been fully clarified,the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention.This review surveyed numerous studies focusing on IBSassociated single nucleotide polymorphisms,and investigated the ethnic disparities revealed by them.The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies.Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural,multi-ethnic,or secondary analyses in IBS,for example,a meta-analysis.Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention,intervention,and treatment of this disease.

Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia

Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.2%)(P < 0.001). The G allele of LDL receptor exon8 c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8 c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders(P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for nonresponse. There was a significant association between LDL receptors exon8 c.1171G>A and HAI(P < 0.011). There was a significant association between LDL receptors exon8 c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype(28.7 ± 4.7 kg/m2) followed by the GA genotype(28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype(26.6 ± 4.3 kg/m2)(P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis(P < 0.001).CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptiansinfected with chronic HCV.

CETP polymorphism confer genetic contribution to centenarians of Hainan,south of China

Objective:In this paper,we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island.Methods:We tested the Taq IB and I405 V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package(Version 19.0).Results:Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P<0.001.Further analysis implied that genotypes B1B1(P<0.001,OR=0.148,95% CI=0.095-0.230) and VV(P<0.001 and OR=0.353,95% CI=0.237-0.525) were significantly different between centenarians and matched controls.The combination of B and V,such as B1B1-II(P<0.001,OR=0.128,95% CI=0.049-0.329),B1B1-IV(P<0.001,OR=0.115,95% CI=0.056-0.237),B1B2-VV(P<0.05,OR=0.534,95% CI=0.310-0.920),and B2B2-VV(P<0.001,OR=0.198,95% CI=0.086-0.453) have significant differences between centenarians and matched healthy individuals from Hainan.Conclusion:Our results implied that allele B1B1 and VV,as well as the combination B1B1-II,B1B1-IV,B1B2-VV and B2B2-VV may contribute to the longevity in centenarians of Hainan,south of China.

interleukin 28B genetic polymorphism and hepatitis B virus infection

Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-&#x003b1; (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B.

The genetic polymorphism of Plasmodium vivax genes in endemic regions of Thailand

Objective:To investigate the genetic polymorphism of Plasmodium vivax(P.vivax) PvCSP and PvMSP1 genes from field isolates at four endemic regions(North,East,West and South) of Thailand.Methods:The 152 P.vivax injected cases from dried blood spots were DMA extracted and confirmed by species-specific primer sets using multiplex PCR method.PvMSPI fragments F2 and F3:PvCSP were gcnotvped using RFLP-PCR method.Resuits:Totally amplified DNA which was multiple genotypes for PvMSP1 F2 and PvMSP1 F3 were 12.50%and 8.55%.respectively while PvCSP was 3.95%.The overall frequency of multiple genotypes was 25%.There were 12 allele tvpes of PvMSP1 F2 using AluI enzyme digestion and 8 size variations were found in P\MSP1 F3.The isolates from western region was highly genetic diverse when compare among all isolates.The predominant variant type of PvCSP gene was \ K2I0 type.Conclusions:The niulliple genotypes are common found in Thailand and it might hide the real genotype.PvCSP does not have extensive genetic diversity in this study.However.PvMSPI marker due to multiple genotypes is difficult In be analyzed.The multiple genotypes findings might stem from population migration and vector species findings.

POLYMORPHISM OF ANGIOTENSIN CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

BACKGROUND： Increased expression of multidrug resistance 1 （MDR1） mRNA in peripheral blood of patients with intractable epilepsy is not due to epilepsy drugs, but epilepsy behavior. Monitoring MDR1 expression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE： To investigate the influence of antiepileptic drugs and seizures on MDR expression in intractable epilepsy, and to analyze the genetic polymorphisms of C3435T in the MDRl gene. DESIGN, TIME AND SETTING： Factorial designs and comparative observations at the experimental center of the Affiliated Hospital of Qingdao Medical College, Qingdao University between October 2003 and October 2004. PARTICIPANTS： A total of 120 subjects were recruited from the epilepsy clinical department of the Affiliated Hospital of Qingdao Medical College. Four groups （n = 30） were classified according to statistical factorial design： intractable epilepsy, treatment response, no treatment, and normal control groups. METHODS： One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES： Expression of MDR1 mRNA in the four groups, and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS： MDRl gene expression was increased in the intractable epilepsy group, due to the factor seizures, but not the antiepileptic drugs. However, the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group, the following genotypes were exhibited： 3 （10%） C/C genotype, 9 （30%） C/T genotype, and 18 （60%） T/T genotype at the site of C3435T, while 4 （13%）, 10 （33%）, and 16 （53%） subjects were determined to express these genotypes in the normal control group, respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group, and 30% and 70% in the normal control group, respectively. However, there was no statistical difference between the groups. CONCLUSION： Results demonstrated that seizures, not antiepileptic drugs, induced MDR1 gene expression in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.

Forecast of the Heterosis of Imported Meat Sheep by Genetic Polymorphism of Microsatellite DNA

Forecast of the heterosis of Small Tail Han sheep crossed with imported meat sheep by genetic polymorphism of microsatellite DNA was done in different sheep breeds. The gene frequency, the polymorphism information contents, the number of effective alleles, the heterozygosity, and the genetic distances were studied in four imported meat sheep and Small Tail Han sheep using five microsatellite loci. The crossing effects on the Small Tail Han sheep with four imported meat sheep were tested. The results indicate that there are genetic polymorphisms at five microsatellite loci in five sheep breeds. Five microsatellite loci can be used for genetic diversity evaluation in sheep breeds. The genetic variability of Dorset is the highest, and that of the Small Tail Han sheep is the lowest in the five sheep breeds. The order of heterosis from large to small in four imported meat sheep by the analysis of genetic relationship is White-Suffolk, Black-Suffolk, Dorset, and Texel. This accords with the testing results of actual heterosis. It is feasible to forecast the heterosis of Small Tail Han sheep crossed with imported meat sheep by genetic polymorphism of microsatellite DNA, which will have an important value for sheep breeding in the future.

SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci

In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.

A single nucleotide polymorphism in SPA TA17 may be a genetic risk factor for Japanese patients with meiotic arrest

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis were identified by microarray analysis of human testicular tissue. One of these is spermatogenesis-associated 17 （SPATA17）. To investigate whether defects in the SPATA17 gene are associated with azoospermia due to meiotic arrest, a mutational analysis was conducted, in which the SPATA17 coding regions of 18 Japanese patients with this condition were sequenced. A statistical analysis was carried out that included 18 patients with meiotic arrest, 20 patients with Sertoli-cell-only syndrome （SCOS） and 96 healthy control men. No mutations were found in SPA TA17. However, three coding single nucleotide polymorphisms （cSNPs： SNP 1-SNP3） were detected in the patients with meiotic arrest. No significant differences in the genotype or allele frequencies of SNP1 and SNP2 were found between patients with meiotic arrest and the others. However, the frequency of the SNP3 allele was significantly elevated in the meiotic arrest group （P 〈 0.05）. This study suggests that SPATA17 may play a critical role in human spermatogenesis, especially in meiosis.

Study of apolipoprotein E genetic polymorphism in patients with atherosclerotic cerebral infarction

Objective: To explore the frequency and significance of ApoE gene polymorphisms in Chinese patients with atherosclerotic cerebral infarction (ACI). Methods: Polymerase chain reaction and gene sequencing, single nucleotide polymorphisms of ApoE gene were used to analyze 33 cases of patients with ACI and 35 controls. Results: The frequencies of ApoE gene single nucleotide polymorphisms 465C/G, 462C/G and 451delC in the ACI group were significantly higher than those in the control group (P<0.05). The prevalence of polymorphism 486G/T in the control group was significantly higher than that in the ACI group ( P = 0.011) . Conclusions: 465C/G,462C/G and 451delC polymorphisms might be associated with ACI.486GT allele might have protective effect on the pathogenesis of ACI.

Application of restriction site amplified polymorphism (RSAP) to genetic diversity in Saccharina japonica

Restriction site amplified polymorphism (RSAP) was used, for the first time, to analyze the genetic structure and diversity of four, mainly cultivated, varieties of the brown alga, Saccharina japonica. Eighty-eight samples from varieties "Rongfu", "Fujian", "Ailunwan" and "Shengchanzhong" were used for the genetic analyses. One hundred and ninety-eight bands were obtained using eight combinations of primers. One hundred and ninety-one (96.46%) were polymorphic bands. Nei's genetic diversity was 0.360, and the coefficient of genetic differentiation was 0.357. No inbreeding-type recession was found in the four brown alga varieties and the results of the "Ailunwan" variety using samples from 2 years showed that the variety was becoming less diverse during the selection inherent in the breeding program. Genetic diversity and cluster analyses results were consistent with these genetic relationships. The results show the RSAP method is suitable for genetic analysis. Continuous inbreeding and selection could reduce the genetic diversity effectively; therefore periodical supervision is required.

A p53 genetic polymorphism of gastric cancer: Difference between early gastric cancer and advanced gastric cancer

AIM: To investigate the role of the polymorphism of p53 codon 72 in early gastric cancer (EGC) and advanced gastric cancer (AGC) in Korean patients. METHODS: DNA was extracted from blood samples of gastric cancer patients (n = 291) and controls (n = 216). In the p53 codon 72 genotypes were determined by PCR-RFLP.RESULTS: Patients with gastric cancer had a significantly higher frequency of the homozygous proline (Pro) allele than the control (P = 0.032). Patients with AGC had a significantly higher frequency of the Arg/Arg (arginine) allele (P = 0.038) than EGC and a similar Pro/Pro allele. The signet ring cell type had a higher frequency of the Pro/Pro allele than other types (P = 0.031). The Pro/Pro genotype carries a 3.9-fold increased risk of developing gastric cancer (95% CI, 1.3-15.4, P = 0.039) when compared to Arg/Arg and Arg/Pro genotypes and to develop EGC is a 5.25 fold increased risk (95% CI, 1.8-19.6, P = 0.021). CONCLUSION: The Pro/Pro genotype of the p53 codon 72 polymorphism carries a higher risk for gastric cancer in general and is also associated with a much higher risk for EGC than AGC.

Effect of ALDH2 Genetic Polymorphism on the Adaptive Change in Alcohol Metabolism Due to Continuous Moderate Alcohol Consumption in Humans

Few studies have assessed the difference in adaptive changes of alcohol metabolism in the case of chronic alcohol consumption pertaining to the genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in humans. To evaluate the influences of ALDH2 genotypes on changes in alcohol metabolism due to continuous alcohol intake, we conducted an intervention study by setting a continuous drinking period between two abstinence periods. The subjects in this study comprised 20 - 25-year-old males, including 15 males carrying ALDH2*1/*1 and 16 carrying ALDH2*1/*2 genotypes. Following the abstinence period of 4 weeks (from day 1 to day 28), all subjects drank commercially available beer (500 ml) every evening for 6 weeks (from day 30 to day 71) and subsequently abstained from drinking again for 4 weeks (from day 73 to day 100). The next morning, after the end of each period, drinking tests (DTs) were performed on each subject (DT1 on day 29, DT2 on day 72, and DT3 on day 101) to examine alcohol metabolism. The subjects drank shochu (a distilled alcoholic beverage), with an ethanol dose of 0.32 g/kg, within 20 minutes after overnight fasting. The alcohol elimination rate in subjects with ALDH2*1/*1 genotype was significantly higher during DT2 after the drinking period as compared with those at both DT1 and DT3 after the abstinence periods, whereas the elimination rate in subjects with ALDH2*1/*2 genotype did not change significantly during 3 DTs. However, blood acetaldehyde levels significantly decreased in subjects with both ALDH2 genotypes during DT2 as compared with those during DT1. The physiological subjective responses to alcohol also significantly decreased during DT2 in subjects with ALDH2*1/*2 genotype. Moreover, serum lipids, gamma-glutamyltransferase (GGT), and uric acid concentrations also varied between subjects with different ALDH2 genotypes due to continuous drinking. These results suggested that ALDH2 polymorphism modified adaptive changes in alcohol metabolism and physiological responses to continuous moderate alcohol consumption.