Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography.

OBJECTIVE: Familial hypercholesterolemia (FH) is characterized by an elevated low-density lipoprotein cholesterol and increased risk of premature coronary artery disease. However, the general picture and mutational spectrum of FH in China are far from recognized, representing a missed opportunity for the investigation. APPROACH AND RESULTS: A total of 8050 patients undergoing coronary angiography were enrolled. The diagnosis of clinical FH was made using Dutch Lipid Clinic Network criteria, and the information of relatives was obtained by inquiring for the probands or from their own medical records of certain clinics/hospitals. Molecular analysis of FH was performed using target exome sequencing in LDLR (low-density lipoprotein cholesterol receptor gene), APOB (apolipoprotein B gene), and PCSK9 (proprotein convertase subtilisin/kexin type 9 gene). As a result, 3.5% of the patients with definite/probable FH phenotype (definite 1.0% and probable 2.5%) were identified. Women FH had fewer premature coronary artery disease (women <60, or men <55 years of age) when compared with men FH (70.6% versus 82.7%; P<0.001), whereas angiographic extension of coronary artery disease was significantly increased with FH diagnosis in both men and women (P<0.001). Patterns of medication use in definite/probable FH were as follows: nontreated, 20.6%; low intensity, 6.0%; moderate intensity, 68.3%; and high intensity, 5.0%. However, none of them had achieved the low-density lipoprotein cholesterol <100 mg/dL. Additionally, mutational analysis was performed in 245 definite/probable FH cases, and risk variants were identified in 115 patients, giving a detection rate of 46.9%. CONCLUSIONS: We showed firsthand a common identification but poor treatment of patients with FH phenotype in Chinese coronary angiography patients. Genetic data in our FH cases might contribute to update the frequency and spectrum of Chinese FH scenarios.

[Screening and identification of 36 new STR loci in human Y chromosome].

133 candidate Y-STR loci were selected from NCBI STS database or by bioinformatics analysis in human Y-chromosome sequence, and were screened among 48 DNA samples around the world. Forty-one Y-STRs with high allelic frequency were validated, 36 of which were first reported. Two hundred haplotypes of the 41 STRs were identified among 200 randomly sampled male individuals in Shanghai, indicating 100% inter-individual discrimination. By network analysis of haplotypes of the 41 STRs among nine Jiang-surname male individuals with no consanguinity within 5 generations from a Jiang-surname individual gathering at Jiangshan, Zhejiang Province, and 7 Jiang-surname male individuals from the random shanghai population, 6 Jiang-surname individuals from Jiangshan were close with only 2-4 STR locus difference. These 41 Y-STR loci provide enough information by which individuals from each other with different early modern family origin can be effectively distinguished. This will promote studies on identification of non-lineal relationship in forensics, ancestry location of oversea Chinese, the surname origin and evolution, origin and migration of modern humans and many other studies of Contemporary Anthropology.

[Relationship between six single nucleotide polymorphisms of angiotensinogen gene and essential hypertension].

OBJECTIVE: To evaluate the relationship of six single nucleotide polymorphisms(SNPs) and their haplotypes of angiotensinogen(AGT) gene to essential hypertension(EH) in Chinese Han population. METHODS: The genotypes in 185 patients with EH and 185 healthy controls were determined by the method of ABI PRISM SNaPshot Multiplex Kit using six AGT gene polymorphisms at position -217(G/A), -152(G/A), -20(A/C) and -6(G/A) in the promoter region and T174M, M235T in exon 2. RESULTS: The distribution of AGT genotypes and alleles frequencies showed no significant difference between the group of EH and group of controls (P>0.05). However, haplotype analysis revealed that H4 haplotype frequency, which included -152A, -20C, -6A and 235T alleles, was significantly increased in the group of EH (P<0.05). CONCLUSION: G-152A, A-20C, G-6A and M235T polymorphisms of AGT gene might play an important role in the occurrence of EH in Chinese Han population.

Single nucleotide polymorphisms in CAPN10 gene of Chinese people and its correlation with type 2 diabetes mellitus in Han people of northern China.

OBJECTIVE: To investigate the distribution of single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in different nationalities of China. Five SNPs were chosen to perform case-control study and haplotype analysis in 156 normal Han people of Northern China and 173 type 2 diabetes. One SNP was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 people). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp. The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese were different from those reported in Mexican American. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control, and the haplotype frequencies in the two groups were not significantly different. No positive results was found in TDT and STDT analysis. CONCLUSIONS: The SNP distribution of CAPN10 gene differs in different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.

[Single nucleotide polymorphisms in CAPN10 gene of Chinese population and its correlation with type 2 diabetes mellitus in Han people of northern China].

OBJECTIVE: To investigate the distribution of the single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in 27 samples of different nationalities in China. 5 SNPs were genotyped with single-base extension (SBE) method to perform case-control study in 156 normal Han people of Northern China and 173 type 2 diabetes and the 3 positive loci reported in the article were performed haplotype analysis. One positive locus was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 cases). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp; The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese was different from that reported in American Mexicans. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control (P > 0.05), and the haplotype frequencies in the two groups were not much different (P > 0.05). There was no positive results in TDT and STDT analysis (P > 0.05). CONCLUSIONS: The SNP distribution of CAPN10 gene varies with different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.