基质金属蛋白酶9基因(-8202A/G)中单核苷酸多态性与胸主动脉瘤和胸主动脉夹层形成相关

Objective: Matrix metalloproteinase 9 plays an important role in the maintenance of the aortic extracellular matrix. Genetic variations that affect protease expression or activity might contribute to thoracic aortic disease. The purpose of this study was to determine whether 3 single nucleotide polymorphisms in the matrix metalloproteinase 9 gene are associated with thoracic aortic aneurysms and dissection. Methods: Genomic DNA was isolated from blood or aortic tissue from 28 patients with degenerative thoracic aortic aneurysms, 60 patients with thoracic aortic dissection, and 111 control patients. The frequency distributions of 3 matrix metalloproteinase 9 single nucleotide polymorphisms(-8202A/G, IVS4+3G/T, and 2003A/G[Q668R]) were determined by using genotyping accomplished with a real-time detection system. Associations between polymorphisms and disease were estimated with odds ratios and their 95%confidence intervals. Results: The frequency of the-8202G allele was significantly higher in patients with thoracic aortic aneurysms and aortic dissection(0.52 and 0.56, respectively) than in control subjects(0.36, P< .001). Patients with thoracic aortic aneurysms or dissection were nearly 5 times more likely than control subjects to have the G allele(adjusted odds ratio, 4.87; 95%confidence interval, 2.04-11.64). There were no significant associations between the IVS4+3G/T or 2003A/G polymorphisms and thoracic aortic disease. Conclusions: The matrix metalloproteinase 9-8202A/G polymorphism is associated with thoracic aortic aneurysms and dissection. Further studies are warranted to elucidate the functional role of the-8202A/G variant in matrix metalloproteinase 9 expression.

A Recursive Algorithm for Offspring's Genotype Frequency of Selfing Population on Multiple Alleles with Limited Loci

This paper studies the offspring＇s genotype frequency of the selfing population on multiple alleles with limited loci.A recursive algorithm is given for it.It is discovered that the genotype frequency of homozygous gene of limited loci increases by generations.Relative increment reduces by generations and the genotype frequency tends to a definite value finally.The genotype frequency of limited loci with hybrid gene tends to 0 finally.But it is possibility that the genotype frequency increases in previous generations then reduces later.It is found that the number of the hybrid gene are more,the speeds tending to 0 are quicker.

Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

AIM: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR146a genes are associated with sporadic colorectal cancer (CRC).METHODS: In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis. RESULTS: The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results. CONCLUSION: Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.

Iron homeostasis and H63D mutations in alcoholics with and without liver disease

MM： To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease. METHODS： One hundred and fifty-three heavy drinkers （defined as alcohol consumption 〉 80 g/d for at least 5 years） were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics （LDA）] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics （NLDA）], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area. RESULTS： Gender ratio was similar in both study groups. LDA patients were older than NLDA patients （52 ± 10 years vs 48 ± 11 years, P = 0.03）. One third and one fifth of the study population had serum transferrin saturation （TS） greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS （51 ± 27 vs 36 ± 13, P 〈 0.001） and ferritin levels （559 ± 607 ng/mL vs 159 ± 122 ng/mL, P 〈 0.001）, and lower total iron binding capacity （TIBC） （241 ± 88 μg/dL vs 279 ± 40 μg/dL, P = 0.001）. The odds ratio for having liver disease with TS greater than 45% was 2.20 （95% confidence interval （CI）： 1.37-3.54）. There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients （0.25 vs 0.16, P = 0.03）. LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients （49.5% vs 31.6%, P = 0.02）. The odds ratio for LDA in patients with H63D mutation was 1.57 （95% CI： 1.02-2.40）. CONCLUSION： The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with liver disease, in parallel with an increased frequency of H63D HFE mutation.

Multidrug resistance protein 3 R652G may reduce susceptibility to idiopathic infant cholestasis

AIM:To evaluate the role of genetic factors in the pathogenesis of idiopathic infant cholestasis.METHODS:We performed a case-control study,in-cluding 78 infants with idiopathic infant cholestasis and 113 healthy infants as controls.Genomic DNA was extracted from peripheral venous blood leukocytes us-ing phenol chloroform methodology.Polymerase chain reaction was used to amplify the multidrug resistance protein 3(MDR3)R652G fragment,and products were sequenced using the ABI 3100 Sequencer.RESULTS:The R652G single nucleotide polymorphism(SNP)was significantly more frequent in healthy infants(allele frequency 8.0%)than in patients(allele frequency 2.60%)(P < 0.05),odds ratio,0.29;95% confidence interval,0.12-0.84.The conjugated bilirubin in patients with the AG genotype was significantly lower than in those with the AA genotype(44.70 ± 6.15 μmol/L vs 95.52 ± 5.93 μmol/L,P < 0.05).CONCLUSION:MDR3 R652G is negatively correlated with idiopathic infant cholestasis.Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis.

No association between IRF3 polymorphism and susceptibility to hepatitis B virus infection in Chinese patients

AIM:To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in inter-feron regulatory factors (IRF3) and the genetic suscep-tibility to chronic hepatitis B virus (HBV) infection.METHODS:We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as controls.Three tagSNPs in IRF3 (rs10415576,rs2304204,rs2304206) were genotyped with the Multiplex SNaPshot technique.The genotype and allele frequencies were calculatedand analyzed.RESULTS:The three SNPs showed no significant geno-type/allele associations with chronic HBV infection.Overall allele P values were:rs10415576,P=0.0908,odds ratio (OR) [95% confidence interval (CI)]=1.1798 (0.9740-1.4291);rs2304204,P=0.5959,OR (95% CI)=1.0597 (0.8552-1.3133);rs2304206,P=0.8372,OR (95% CI)=1.0250 (0.8097-1.2976).Overall genotype P values were:rs10415576,P=0.2106;rs2304204,P=0.8458;rs2304206,P=0.8315.There were no statisti-cally significant differences between patients with chron-ic HBV infection and controls.Haplotypes generated by these three SNPs were also not significantly different between the two groups.CONCLUSION:The three tagSNPs of IRF3 are not asso-ciated with HBV infection in the Han Chinese population.

-449 C>G polymorphism of NFKB1 gene,coding nuclear factor-kappa-B,is associated with the susceptibility to ulcerative colitis

AIM:To clarify the association between a polymorphism-449 C>G(rs72696119) in 5'-UTR of NFKB1 with ulcerative colitis(UC).METHODS:The studied population comprised 639 subjects,including patients with UC(UC cases,n = 174) and subjects without UC(controls,n = 465).We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS:The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%,respectively(P = 0.10).Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls(P = 0.017),and the GG homozygote was significantly associated with susceptibility to UC [odds ratio(OR),1.88;95%CI,1.13-3.14].In male subjects,the GG homozygote was associated with an increased risk for UC(OR,3.10;95%CI,1.47-6.54;P = 0.0053),whereas this association was not found in female subjects.In addition,the GG homozygote was significantly associated with the risk of non-continuous disease(OR,2.06;95%CI,1.12-3.79;P = 0.029),not having total colitis(OR,2.40;95%CI,1.09-3.80,P = 0.040),disease which developed before 20 years of age(OR,2.80;95%CI,1.07-7.32,P = 0.041),no hospitalization(OR,2.28;95%CI,1.29-4.05;P = 0.0090) and with a maximum of 8 or less on the UCDAI score(OR,2.45;95%CI,1.23-4.93;P = 0.022).CONCLUSION:Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC.This polymorphism influences the susceptibility to and pathophysiological features of UC.

Risk modification of colorectal cancer susceptibility by interleukin-8-251T>A polymorphism in Malaysians

AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8-251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. METHODS: Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8-251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ 2 tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. RESULTS: On comparing the frequencies of genotypesof patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69,P = 0.003). CONCLUSION: Variant allele and genotype of IL-8 (-251 T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

Ku80 gene G-1401T promoter polymorphism and risk of gastric cancer

AIM:To evaluate the possible relationship between the Ku80 gene polymorphism and the risk of gastric cancer in China.METHODS:In this hospital-based case-control study of gastric cancer in Jiangsu Province,China,we investigated the association of the Ku80 G-1401T (rs828907) polymorphism with gastric cancer risk.A total of 241 patients with gastric cancer and 273 age-and sexmatched control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism.RESULTS:The frequencies of genotypes GG,GT and TT were 65.6%,22.8% and 11.6% in gastric cancer cases,respectively,and 75.8%,17.6% and 6.6% in controls,respectively.There were significant differences between gastric cancer and control groups in the distribution of their genotypes (P=0.03) and allelic frequencies (P=0.002) in the Ku80 promoter G-1401T polymorphism.CONCLUSION:The T allele of Ku80 G-1401T may be associated with the development of gastric cancer.

Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People

Objective To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 （PPARγ2） promoter and coronary heart disease （CHD）. Methods This case-controlled study was conducted in nondiabetic Chinese Han people, which enrolled 455 patients with CHD （cases） and 693 subjects without CHD （controls）. Data of clinical indexes were collected, including height, body weight, waist circumstance, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, smoking, drinking, physical activity, as well as body mass index （BMI）. Fasting blood glucose （FBG）, plasma total cholesterol （TC） and triglyceride （TG） levels were measured. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T, allelic frequency, clinical indexes, and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model. Results The genotype frequencies of CC, CT and TT in PPARγ2 promoter C-689T were 89.7%, 9.9% and 0.4% in the case group, and 93.1%, 6.6% and 0.3% in the control group, respectively （CC vs. CT＋TT, χ^2= 6.243, P=0.041）. Carriers of -689T allele （n=95） had significantly higher TC level than non-carriers （n=1053） （5.12±1.26 vs. 4.76±1.22 mmol/L, P=0.001）. Male carriers of -689T allele （n=51） were significantly higher in waist circumference, body weight, TC and TG than male non-carriers （n=656） （all P〈0.05）. In subjects whose BMI was over 25 kg/m2, carriers of -689T allele （n=82） had significantly higher levels of waist circumference, BMI, SBP and TC than non-carriers （n=231） （all p〈0.05）. The -689T allele was an independent risk factor for CHD （OR=1.668, 95%CI： 1.031-2.705, P=0.037） after adjusting for age, gender, waist circumference, body weight, BMI, smoking, physical activities, SBP, DBP, FBG, TC and TG level. Conclusion These data support the hypothesis that the -689T allele is associated with an increased risk of CHD, in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.

Low Frequencies of CCR5-Δ32 and CCR5-m303,but High Frequencies of CCR2-641 and SDF1-3'A Alleles in Indigenous Ethnic Groups in China's Mainland

Objective: The aim in this study was to identify the allelicfrequencies of the chemokine (SDF1-3'A) and chemokinereceptor (CCR5△32, CCR5m303 and CCR2-64I) genesresistant to HIV-1 infection and/or disease progression inindigenous Chinese populations. Methods: By using QIAamp DNA Blood Mini Kit, thegenomic DNA samples were purified from whole peripheralblood of healthy individuals (n=2067) from Han, Uygur,Mongolian and Tibetan ethnic groups, as well as Han patientsincluding HIV-1 carriers (n=330), patients with other sexuallytransmitted diseases (STDs, n=259) and intravenous drugusers (IVDUs, n=125). The allelic polymorphisms wereidentified by means of PCR or PCR-RFLP analyses. Thesequences of randomly selected amplified PCR products werefurther confirmed by direct DNA sequencing. Results: The mutant frequencies were identified to be0%～3.48% for CCR5△32, 0% for CCR5m303,19.15%～28.79% for CCR2-64 and 19.10%～28.73% for SDF1-3'A alleles, respectively, in Chinese healthy individuals fromfour ethnic groups. Our findings indicated the allelicfrequencies vary among the different ethnic groups.Furthermore, the HIV-1 carriers, STD cases and IVDUs (all ofHan ethnicity) were found to have the allelic frequencies of0%～0.19% (CCR5△32), 0% (CCR5m303), 19.31%～20.45%(CCR2-64) and 25.61%～26.83% (SDF1-3'A) with minorvariations in their frequencies between the patients andhealthy Han groups. There was no CCR5-m303 mutationfound in any subject in this study. Conclusion: The examined subjects of four Chinese ethnicorigins showed lower frequencies of CCR5△32 andCCR5m303 alleles, but higher frequencies of mutant CCR2-64I and SDF1-3'A alleles compared to those identified innorthern-European and American Caucasians. Thesignificance of the different frequencies and polymorphisms ofthe above alleles in Chinese populations needs to be furtherexamined in HIV-1/AIDS diseases.

Coagulation factor Ⅶ gene polymorphisms are not associated with the occurrence or the survival of hepatocellular carcinoma:a report of 37 cases

Objective: Coagulation factor VII(FVII) triggers the extrinsic pathway of blood coagulation. In our previous study, we showed that FVII plays an important role in tumorigenesis of hepatocellular carcinoma(HCC). However, the role of FVII polymorphism in HCC is still unknown. The present study aimed to investigate the relationship between HCC carcinogenesis and single nucleotide polymorphism of FVII.Methods: Thirty-seven HCC patients and 30 healthy donors were recruited in this study. Four common FVII gene polymorphisms– a decanucleotide insertion at position –323(–323 ins10-bp), a G to T substitution at position –401(–401 G/T), a G to A substitution at position –402(–402 G/A), and a T to C substitution at position –122(–122 T/C) – were analyzed by sequencing or commercialized assays using genomic DNA isolated from blood samples. Clinicopathological parameters between control and HCC subjects were compared according to the specific genotypes.Results: The most common nucleotide variation was –402 G/A. However, no statistically significant difference was observed between healthy controls and HCC subjects for all four polymorphisms in terms of genotype distribution and allele frequencies,indicating that these polymorphisms may not affect HCC tumorigenesis. Furthermore, no association was found between–402 G/A polymorphisms and tumor stage, recurrence, and overall survival.Conclusions: Our results indicate that FVII polymorphisms may not be a key factor that clinically impact tumorigenesis and outcomes of HCC, although further investigations should be conducted to confirm our findings.

Polymorphisms of clip domain serine proteinase and serine proteinase homolog in the swimming crab Portunus trituberculatus andtheir associationwith Vibrio alginolyticus

Clip domain serine proteases （cSPs） and their homologs （SPHs） play an important role in various biological processes that are essential components of extracellular signaling cascades, especially in the innate immune responses of invertebrates. Here, polymorphisms of PtcSP and PtSPH from the swimming crab Portunus tritubereulatus were investigated to explore their association with resistance/ susceptibility to Vibrio alginolyticus. Polymorphic loci were identified using Clustal X, and characterized with SPSS 16.0 software, and then the significance of genotype and allele frequencies between resistant and susceptible stocks was determined by a Zz test. A total of 109 and 77 single nucleotide polymorphisms （SNPs） were identified in the genomic fragments of PtcSP and PtSPH, respectively. Notably, nearly half of PtSPH polymorphisms were found in the non-coding exon 1. Fourteen SNPs investigated were significantly associated with susceptibility/resistance to I1. alginolyticus （P〈0.05）. Among them, eight SNPs were observed in introns, and one synonymous, four non-synonymous SNPs and one ins-del were found in coding exons. In addition, five simple sequence repeats （SSRs） were detected in intron 3 of PtcSP. Although there was no statistically significant difference of allele frequencies, the SSRs showed different polymorphic alleles on the basis of the repeat number between resistant and susceptible stocks. After fiarther validation, polymorphisms investigated here might be applied to select potential molecular markers ofP. trituberculatus with resistance to I1. alginolyticus.

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population

Objectives To study the association of single nucleotide polymorphism （SNP） rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases （PCAD） in Chinese Hun population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography （CAG） results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium （P 〉 0.05）. The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant （P = 0.042）. The genotype distribution ofrs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model （OR： 0.828, 95% CI： 0.711-0.964, P = 0.014）, and in the dominant model （OR： 0.753, 95% CI： 0.591-0.958, P = 0.021）. After removing the confound- ing variables, the rs2076185 polymorphisms was associated with PCAD in the additive model （OR： 0.775, 95% CI： 0.648-0.928, P = 0.005）, in the dominant model （OR： 0.698, 95% CI： 0.527-0.925, P = 0.012）, and in the recessive model （OR： 0.804, 95% CI： 0.538-0.983, P - 0.038）. Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Hun population, therefore it could be a coronary artery diseases protective factor in Chinese Hun population.

Identification of K-Casein Polymorphism in Bali Cattle

The present study was conducted to identify K-casein （Kappa-casein） polymorphism in the Bali cattle （Bos sondaicus）. A 780 bp specific fragment of K-casein gene spanning from the forth exon region （517 bp） to forth intron （263 bp） was amplified from 60 individuals from the Bali Cattle Breeding Centre in Jembrana regency, Bali province. PCR-RFLP analysis with HindlII indicated that only the BB genotype was found at locus I, while with PstI indicated that two genotypes AA and AB were found at the k-casein locus If. The frequencies of A and B alleles at locus II were 0.91 and 0.09, respectively. Mutations in locus II did not change the amino acid coding （silent mutation）. At locus I, comparison with allele frequencies in other cattle breeds indicates that frequencies in Bali cattle （Bos sondaicus） are significantly different from those observed in Bos taurus and Bos indicus breeds.

Genetic Association Study of KCNB1 Gene with the Susceptibility of Hypertension Related LVH （Left Ventricular Hypertrophy） Patients in Malaysia

LVH （Left ventricular hypertrophy） is an independent risk factor for the development of heart failure, cardiac arrhythmias and stroke. A recent genome-wide association study reported the involvement of a candidate gene namely KCNBI in mechanism for development of LVH in hypertension. This study aimed to replicate the finding by investigating the genetic association of KCNBI gene among the hypertensive LVH patients from Malaysia. We genotyped a SNP （single nucleotide polymorphism） located in KCNBI namely, rs6063397 among 200 subjects consisting of61 LVH and 139 non LVH patients using Sanger sequencing method. Statistical analysis revealed no significant association between the L VH susceptibility between the allele and genotype frequencies （P = 0.2719 and 0.4768, respectively）. This finding suggests that KCNBI may not playa role in LVH susceptibility in hypertensive patients in Southeast Asian populations.

Genotypes and polymorphisms of mutant CCR5-△32,CCR2-64I and SDF1-3'A HIV-1 resistance alleles in indigenous Han Chinese

Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.

High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China

OBJECTIVE: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC. METHODS: Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques. RESULTS: LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells. CONCLUSION: Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.

β-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level in Chinese stroke patients

Abstract Objectives To investigate the relationship between the β-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level and to determine the influence of the mutation on ischemic stroke. Methods Ninety-one patients (63.5±10.1 years) with ischemic stroke and 74 elderly control subjects (60.6±10.8 years) without any thromboembolic events and 98 healthy blood donators as young control (37.5±13.3 years) were enrolled in this trial. The β-fibrinogen gene -455A/G polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme Hae Ⅲ, while plasma fibrinogen levels were obtained from the prothrombin time (PT) assay. For statistical analysis, the parameters were compared between any two different groups by the unpaired Student’s t test and the Chi-square test. Before analysis, log transformations for concentrations of fibrinogen were carried out.Results H2 allele frequency was higher in male ischemic stroke patients than in the elderly control (22.7% vs 7.1%, χ 2=5.56, P【0.02). There was no significant difference between the female groups. In those patients without any thromboembolic events (both elderly and young control groups), the frequency of H2 decreased with age (≤40, 21.3%; 41-59, 15.4%; and ≥60, 10.2%). In the male elderly and young control groups, the level of plasma fibrinogen was lower in the H1H1 genotype (287±96*!mg/dl and 234±58*!mg/dl) than in H1H2 and H2H2 (331±44*!mg/dl and 307±55*!mg/dl; t=2.53 and 9.67, P【0.05). In the female elderly groups, this tendency was not found.Conclusion Plasma fibrinogen expression is affected by the β-fibrinogen gene -455A/G polymorphism, and the H2 allele may be a risk factor for ischemic stroke in Chinese males.

Detecting polygenic selection in marine populations by combining population genomics and quantitative genetics approaches

Highly fecund marine species with dispersive life-history stages often display large population sizes and wide geographic distribution ranges. Consequently, they are expected to experience reduced genetic drift, efficient selection fueled by frequent adaptive mutations, and high migration loads. This has important consequences for understanding how local adaptation proceeds in the sea. A key issue in this regard, relates to the genetic architecture underlying fitness traits. Theory predicts that adaptation may involve many genes but with a high variance in effect size. Therefore, the effect of selection on allele frequencies may be substantial for the largest effect size loci, but insignificant for small effect genes. In such a context, the performance of population genomic methods to unravel the genetic basis of adaptation depends on the fraction of adaptive genetic variance explained by the cumulative effect of outlier loci. Here, we address some methodological challenges associated with the detection of local adaptation using molecular approaches. We provide an overview of genome scan methods to detect selection, including those assuming complex demographic models that better describe spatial population structure. We then focus on quantitative genetics approaches that search for genotype-phenotype associations at different genomic scales, including genome-wide methods evaluating the cumulative effect of variants. We argue that the limited power of single locus tests can be alleviated by the use of polygenic scores to estimate the joint contribution of candidate variants to phenotypic variation.