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Objective: To identify the casual mutation of a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship., Methods: The coding exons of 26 reported disease genes were sequenced by targeted resequencing in the proband and the identified mutation were detected with bi-directional Sanger sequencing in all family members and 307 healthy controls. The genotype-phenotype correlation was analyzed in the family., Results: A missense mutation (c.2191C > T, p. Pro731Ser) in the 20th exon of MYH7 gene was identified. This mutation was absent in 307 healthy controls and predicted to be pathogenic by PolyPhen-HCM. Totally 13 family members carried this mutation, including 10 patients with HCM and 3 asymptomatic mutation carriers. The proband manifested severe congestive heart failure and 8 patients expressed various clinical manifestations of heart failure, including dyspnea, palpitations, chest pain, amaurosis or syncope. Five patients were diagnosed as HCM at the age of 16 or younger. One family member suffered sudden cardiac death., Conclusions: The Pro731Ser of MYH7 gene mutation is a causal and malignant mutation linked with familiar HCM.

Objective: To investigate the effect of environmental risk factors on the development of stroke., Methods: With the use of cold-stimuli plus high-salt intake as environmental risk factors, a hypertension model with the complication of stroke was established in rats, then, a new technique, suppression subtractive hybridization (SSH), was used to identify the differential genes which specifically expressed in total cerebrum tissue of rat in each group. Comparison was made between control group and stroke group., Results: By the application of SSH, a total of 576 clones were generated in this study from two subtractive libraries, among them 456 clones were usable and were analyzed. Genes for cell/organs defense were down-regulated in stroke group and metabolism transcripts were shown to be up-regulated (P<0.01)., Conclusion: Cell/organs defense genes may play important roles in the development of stroke. The above findings suggested that environmental risk factors could genetically alter individual sensitivity to stroke.

Objective: Investigate the distribution and characteristics of 5'pentanucleotide TTTTA repeat (PNTR) polymorphism of apolipoprotein (a) [apo (a)] gene among Chinese patients with myocardial infarction (MI) and cerebral infarction, and its relationship to plasma lipoprotein (a) [Lp (a)] level., Methods: DNA was extracted from the peripheral blood of 438 patients with myocardial infarction (MI, documented angiographically) and 218 controls, and 809 patients with cerebral infarction (documented by CT) and 1 817 controls. Plasma Lp (a) level was measured by ELISA. PNTR polymorphism of apo (a) gene was determined by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis., Results: Eight alleles and 29 genotypes in apo (a) PNTR were detected in the four groups. The frequency of (TTTTA)(4 - 7) allele in the cerebral infarction group was 7.0%, significantly higher than that in control group (5.4%, P < 0.05). The frequency of genotype (TTTTA)(5/8) in MI group was 13.2%, significantly higher than that in the control group (7.8%, P < 0.05). No significant difference was seen in other alleles and genotypes among different groups (all P > 0.05). The level of triglyceride (TG) in patients with MI was 5.13 mmol/L +/- 1.15 mmol/L, significantly higher than that in controls (4.90 mmol/L +/- 0.99 mmol/L, P < 0.05). The level of TG in patients with cerebral infarction was 1.84 mmol/L +/- 1.36 mmol/L, not significantly different from that in controls (1.83 mmol/L +/- 1.51 mmol/L). The level of total cholesterol (TC) in patients with MI was 4.85 mmol/L +/- 1.04 mmol/L, significantly lower than that in controls (4.97 mmol/L +/- 1.00 mmol/L, P < 0.001). The level of TC in patients with cerebral infarction was 1.97 +/- 1.11 mmol/L, not significantly different from that in controls (1.79 mmol/L +/- 1.23 mmol/L). A negative correlation between the number of PNTR and Lp (a) level was observed in both MI group (P < 0.001) and cerebral infarction group (P < 0.01), and not in the control group. Small fragment repeat of apo (a) PNTR was correlated with cerebral infarction (OR = 1.4, 95% CI: 1.040 approximately 1.910), not significantly with MI (P > 0.05). Multiple logistic regression analysis showed that individuals with plasma Lp (a) > 300 mg/L had higher risk of MI (OR = 2.4, 95% CI: 1.630 - 3.594), and a higher risk of cerebral infarction (OR = 1.6, 95% CI: 1.013 - 2.021) after adjustment for age, sex, SBP, DBP, BMI, smoking, TC, TG, HDL-C, LDL-C and Glu., Conclusion: Plasma Lp (a) is an independent risk factor for MI and cerebral infarction. PNTR of apo (a) gene was negatively correlated with Lp (a) levels both in MI group and cerebral infarction group. Association with PNTR genotype was only found in cerebral infarction, but not in MI.

Objective: To detect the association among calpain-10(CAPN-10) gene polymorphism, hypentension and hyperglycemia., Methods: 378 individuals in the present study were the second generation offsprings of 187 hypentensives and 19 1 nonhypertensives. Fasting plasma glucose (FPG), insulin, triglyceride and fibrinogen were determined. The polymorphism of UCSNP-43 and UCSNP-44 of CAPN 10 gene were analysed with PCR-SSCP method., Results: (1)The frequency of G/G geno type of UCSNP-43 was higher in the second generation offsprings of the hypertensives than that in the nonhypertensive controls(86.6%, 75.4%, P < 0.05). (2) The frequenncy of G/G genotype of UCSNP-43 was higher in the hypertensive parents of the second generation offsprings in the hypertensive groups than that in the normotensive parent of the second generation offsprings of the nonhypertensive control groups (OR = 2.84, P = 0.01). After adjustment of age, sex and body mass index (BMI), the frequency of G/G genotype in the highest FPG-quartiles (FPG 5.42 +/- 0.1mmol/L) was much more than that in the lowest FPG quartiles (FPG 4.09 +/- 0.3 mmol/L) with OR of 3.32., Conclusions: Polymorphism of UCSNP-43 in CAPN-10 gene might be one of the genetic factors contributing to hypertension and diabetes mellitus in the population in Daqing city. It may be a predictor of type 2 diabetes mellitus (T2DM) in the decendents of hypertensives.