The major role of DNA polymerase ? was thought to be limited in its involvement in short patch base excision repair by removing 5'-deoxyribose phosphate and base insertion. However, the recent researches indicate that polymerase ? might take part in a wide spectrum of DNA metabolism reactions, including long patch base excision repair, DNA replication, recombination, meiosis and transleisional DNA synthesis. Because of its wide and important cellular function, an inappropriate intracellular polymerase ? level might be associated with genomic instability. Down-regulation or mutation of polymerase ? is mutagenic due to deficient in DNA repair, while overexpression of this error-prone ? polymerase might perturb the normal function of other accurate polymerases and cause genomic instability as well.

Objective To screen the mutation in P and 7 subunit of epithelial sodium channel (ENaC) gene in the relatives of a patient diagnosed as Liddle's syndrome. Methods In a family of three generations, seven family members were affected with hypertension, among them a girl aged 14 years was diagnosed as Laddie's syndrome and her mother and maternal grandsire died of stroke at thirty-eight years. Peripheral blood samples were collected from all living members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the final exon of the ? ENaC (codon 513-638) and ? ENaC (codon 524-631 )gene. PCR products were purified and subjected to direct DNA sequencing. Results Genetic analysis of the ? ENaC gene revealed a missense mutation of CCC (Pro) to TCC (Ser)at codon 616 in the index case and two other family members. In these three family members, a new variant of GAC (Asp) to CAC(His) at codon 632 was found, which was linked with 616 (Ser) . This variant was not detected by direct sequencing the final exon of ? ENaC gene in 150 unrelated subjects. Through clinical examinations and biochemical measurement, thSese two mutation carriers' biochemical characteristics were all concordant with Liddle's syndrome. Neither mutation could be detected in other members of this family. The mutation TGG(Trp)573TAG(Term) of ? ENaC gene could not be found in this family either. Conclusions (1) Screening for specific mutations of ENaC in relatives of patients affected with Liddle's syndrome can be used to identify previously unrecognized cases within families. (2) A new missense mutation in the ? ENaC gene is found in this family.

OBJECTIVETo investigate the relationship between blood pressure variability, overweight or obesity in patients with essential hypertensive.

METHODSA hundred ninety-one patients with essential hypertension were divided into three groups: normal, overweight and obese according to body mass index (BMI). The characteristics of the variability of 24-hour ambulatory blood pressure monitoring (ABPM) in three groups were compared.

RESULTSBlood pressure overload and variability increased parallel with the increase of BMI. In overweight group, the variabilities of systolic blood pressure at night (nSBPSD) increased 14.10%, the variabilities of diastolic blood pressure at night (nDBPSD) increased 13.15% and the variabilities of mean arterial pressure at night (nMAPSD) increased 15.92% respectively. In the obese group, the above three variabilities increased more significantly (compared to normal group P < 0.05-0.01). However, increases of the three blood pressure variabilities were observed only in the male patients.

CONCLUSIONSThe overweight or obesity increased the blood pressure overload and variabilities in patients with essential hypertension. The increases of blood pressure variabilities were observed only in male patients and at night.

Adult ; Aged ; Blood Pressure ; Body Mass Index ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Obesity ; physiopathology ; Sex Factors

OBJECTIVETo investigate the genetic linkage between several cytokine and cytokine-related receptor gene loci and essential hypertension (EH) in Chinese.

METHODSLinkage between seven genetic markers and EH in 95 Chinese nuclear families with EH (including 477 subjects) was analyzed using a technique of fluorescence-based gene scan with DNA short tandem repeat loci. These markers were selected from the chromosomal regions nearby eight cytokines and their receptor genes. The two-point non-parametric linkage analysis (NPL), maximum Lod score and transmission/disequilibrium test (TDT) with GENEHUNTER software package were used in this study.

RESULTSResult of TDT showed significant transmission disequilibrium between D14S61 and EH (Chi square 14.29,P=0.00016) although NPL and Lod score revealed no significant linkage (Z=0.78, P>0.05 and Lod score =0.72 respectively) at this locus. No linkage between other loci typed and EH was found by the three genetic analysis methods (P>0.05 or Lod score<-1).

CONCLUSIONAlleles at D14S61 were of significant transmission disequilibrium in affected siblings. Transforming growth factor beta 3 is 0.1 cM away from D14S61, which suggests that the relationship between genes at or near this regions and EH needs to be further explored.

Adult ; Alleles ; Blood Glucose ; metabolism ; Blood Pressure ; physiology ; Body Mass Index ; China ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cytokines ; genetics ; DNA ; genetics ; Family Health ; Female ; Genetic Linkage ; Humans ; Hypertension ; blood ; genetics ; physiopathology ; Linkage Disequilibrium ; Lod Score ; Male ; Microsatellite Repeats ; Middle Aged ; Receptors, Cytokine ; genetics ; Triglycerides ; blood

OBJECTIVETo verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families.

METHODSA genetic linkage study focused on chromosome 2 was performed on 240 Chinese families containing 856 patients with essential hypertension. A total of 1080 individuals were genotyped using 9 highly polymorphic microsatellite markers around the candidate regions on chromosome 2 with an average spacing of 5 cM. Non-parametric linkage (NPL), parametric linkage analysis and transmission-disequilibrium test (TDT) with the GENEHUNTER software were used to assess evidence for linkage.

RESULTSLinkage of a region on chromosome 2 around D2S151 and D2S142 with hypertension was confirmed by different statistical methods (NPL, LOD score and TDT). However, the linkage of D2S168 could not be replicated in this extension study.

CONCLUSIONSThe data suggest that a region on chromosome 2 at or near the loci of D2S142 and D2S151 may harbor genes responsible for the development of essential hypertension in Chinese.

Alleles ; China ; Chromosomes, Human, Pair 2 ; genetics ; Family Health ; Female ; Gene Frequency ; Genetic Linkage ; Humans ; Hypertension ; genetics ; Linkage Disequilibrium ; Male ; Microsatellite Repeats

OBJECTIVETo study the contribution of genetic factors to the variance of serum leptin concentration in healthy, normotensive twins.

METHODSA total of 57 pairs of twins were investigated: 28 female and 19 male pairs of monozygotic(MZ) twins, and 6 female and 4 male pairs of dizygotic(DZ) twins. The zygosity of twins was determined by comparing the concordance of the genotype of nine fluorescence-labeled microsatellite markers. The genetic analysis was performed using the variance-based method. Serum leptin levels were determined in duplicate by a radioimmunoassay Kit (Linco Research, Inc., St. Charles, Missouri) as previously described.

RESULTSThe test of genetic variance revealed a significantly larger within-pair variance of serum leptin in the DZ twins, in comparison with the MZ twins. The corresponding heritability for serum leptin was 8%. Adjusted for BMI, gender, and uric acid (UA), the heritability for serum leptin was 0.18%. Log leptin correlated significantly with blood pressure (SBp r=0.355 P<0.001; DBp r=0.339 P<0.001). Stepwise multiple linear regression analysis revealed that only BMI, gender and UA were linked independently to serum leptin levels(R(2)=0.788, P<0.001).

CONCLUSIONThe above data indicate that environmental factors other than genetic factors are important determinants of leptinemia in normal subjects.

Adolescent ; Adult ; Body Mass Index ; Female ; Genotype ; Humans ; Leptin ; blood ; genetics ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; Twins, Dizygotic ; genetics ; Twins, Monozygotic ; genetics