Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases

BACKGROUND Genetic factors play an important role in neonatal hyperbilirubinemia(NH)caused by genetic diseases.AIM To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases.METHODS This was a retrospective cohort study.One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College.A 24-gene panel was used for gene sequencing to analyze gene mutations in patients.The data were analyzed via Statistical Package for the Social Sciences 20.0 software.RESULTS Seventeen frequently mutated genes were found in the 105 patients.Uridine 5'-diphospho-glucuronosyltransferase 1A1(UGT1A1)variants were identified among the 68 cases of neonatal Gilbert syndrome.In patients with sodium taurocholate cotransporting polypeptide deficiency,the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp(SLC10A1).Adenosine triphosphatase 7B(ATP7B)mutations primarily occur in patients with hepatolenticular degeneration(Wilson's disease).In addition,we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group,whereas mutations in SLC10A1,ATP7B,and heterozygous 851del4 mutation were more common in the low-risk group.CONCLUSION Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

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.

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 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 cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.

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.

GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.

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）

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

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.

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.

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

Genetic Polymorphism of Milk Protein and Their Relationships with Milking Performances in Chinese Yak

The milk protein polymorphisms were typed by polyacrylamide gel electrophoresis (PAGE)from 109 Maiwa and 100 Jiulong yaks, and the relationships among milk protein polymorphisms,milking traits and milk protein compositions were studied. The results showed thatβ-CN,κ-CN andα-La were monomorphic,αs1-CN andβ-Lg were polymorphic, the dominantgenes were αs1-CN D and β-Lg E,respectively. The frequencies of αs1-CN D were 0.8073and 0.6000 and β-Lg E were 0.9770 and 0.9700 in two populations respectively.The meanheterozygosities were 0.1021 and 0.1867 in two populations. No significant effects onmilking traits and milk protein compositions were observed except for αs1-CN locus onfat percentage in Jiulong yak.

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.

Genetic polymorphisms of MAFK, encoding a small Maf protein, are associated with susceptibility to ulcerative colitis in Japan

To investigate whether single nucleotide polymorphisms in maf protein K (MAFK), which encodes the MAFK, lead to increased susceptibility to ulcerative colitis in the Japanese population. METHODSThis case control study examined the associations between MAFK single nucleotide polymorphisms (rs4268033 G>A, rs3735656 T>C and rs10226620 C>T) and ulcerative colitis susceptibility in 174 patients with ulcerative colitis (UC) cases, and 748 subjects without no lower abdominal symptoms, diarrhea or hematochezia (controls). In addition, as the second controls, we set 360 subjects, who have an irregular bowel movement without abnormal lower endoscopic findings (IBM controls). RESULTSThe genotype frequency of rs4268033 AA and allelic frequency of the rs4268033A allele were significantly higher in the UC cases than in both controls (P = 0.0005 and < 0.0001, P = 0.015 and 0.0027 vs controls and IBM controls, respectively). Logistic regression analysis after adjustment for age and gender showed that the rs4268033 AA and rs3735656 CC genotypes were significantly associated with susceptibility to UC development (OR = 2.63, 95%CI: 1.61-4.30, P = 0.0001 and OR = 1.81; 95%CI: 1.12-2.94, P = 0.015, respectively). Similar findings were observed by the comparison with IBM controls. In addition, the rs4268033 AA genotype was significantly associated with all phenotypes of UC except early onset. There was no significant association between rs10226620 and ulcerative colitis. CONCLUSIONOur results provide the first evidence that MAFK genetic polymorphisms are significantly associated with susceptibility to UC development. In particular, rs4268033 is closely associated with an increased risk for the development of UC.