Heterozygous familial hypercholesterolemia in Hong Kong Chinese. Study of 252 cases.

BACKGROUND: Earlier studies reported that Chinese subjects with heterozygous familial hypercholesterolemia (heFH) living in Mainland China or in Western countries had lower plasma low-density lipoprotein cholesterol (LDL-C) levels and lower prevalence of xanthomata or coronary heart disease (CHD) than Caucasians with heFH and a greater proportion went unrecognized. We characterized the features of Hong Kong Chinese with heFH identified by cascade screening. METHODS: Potential probands with primary hypercholesterolemia manifesting total cholesterol (TC) greater than 7.5 mmol/L or LDL-C greater than 4.9 mmol/L were selected from a lipid clinic in a public hospital in Hong Kong. After screening of 132 unrelated potential probands and their relatives, 252 subjects from 87 pedigrees were clinically diagnosed as heFH. RESULTS: In 252 heFH patients (mean age 37 ± 17 years, 100 males), the plasma TC and LDL-C were 9.1 ± 1.5 mmol/L and 7.2 ± 1.5 mmol/L, respectively. In subjects aged ≥ 18 years, the prevalence of xanthomata and corneal arcus was 40.6% and 81.2% in males, and 54.8% and 66.9% in females respectively. The overall incidence of CHD was 9.9% in males and 8.5% in females in patients aged over 18 years with CHD history available. Multiple logistic regression analysis showed that advanced age and presence of xanthelasmata were significantly associated with increased risk of CHD. CONCLUSIONS: This study is the first to characterize the epidemiologic features of heFH in Hong Kong Chinese, which provides new population-specific information on this genetic disorder. This may presage how this condition will manifest in China in the near future.

Protective effects and potential mechanisms of Pien Tze Huang on cerebral chronic ischemia and hypertensive stroke.

BACKGROUND: Stroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH), a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats. METHODS: The effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR) and stroke prone SHR (SHRsp) were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA) and immunostaining. RESULTS: Pien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCR2 in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS) damage and possibly subsequent cell death (caspase 3 assay) as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum. CONCLUSION: Pien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria.

Molecular evidence of the neuroprotective effect of Ginkgo biloba (EGb761) using bax/bcl-2 ratio after brain ischemia in senescence-accelerated mice, strain prone-8.

In the present studies, we investigated the molecular mechanism of one of the active ingredients of Ginkgo biloba, EGb761, to affect the levels of several apoptotic markers in six brain regions following global ischemia in senescence-accelerated mice. A 4-day treatment with EGb761 significantly decreased bax/bcl-2 ratios in all brain regions in both young and aged mice. Our findings indicate that the bax/bcl-2 ratio provides a suitable index of apoptosis and modulation of these markers may explain the neuroprotective action of EGb761.

A susceptibility locus for myopia in the normal population is linked to the PAX6 gene region on chromosome 11: a genomewide scan of dizygotic twins.

Myopia is a common, complex trait with considerable economic and social impact and, in highly affected individuals, ocular morbidity. We performed a classic twin study of 506 unselected twin pairs and inferred the heritability of refractive error to be 0.89 (95% confidence interval 0.86-0.91). A genomewide scan of 221 dizygotic twin pairs, analyzed by use of optimal Haseman-Elston regression methods implemented by use of generalized linear modeling, showed significant linkage (LOD >3.2) to refractive error at four loci, with a maximum LOD score of 6.1 at 40 cM on chromome 11p13. Evidence of linkage at this locus, as well as at the other linkage peaks at chromosomes 3q26 (LOD 3.7), 8p23 (LOD 4.1), and 4q12 (LOD 3.3), remained the same or became stronger after model fit was checked and outliers were downweighted. Examination of potential candidate genes showed the PAX6 gene directly below the highest peak at the 11p13 locus. PAX6 is fundamental to identity and growth of the eye, but reported mutations usually result in catastrophic congenital phenotypes such as aniridia. Haplotype tagging of 17 single-nucleotide polymorphisms (SNPs), which covered the PAX6 gene and had common minor allele frequencies, identified 5 SNPs that explained 0.999 of the haplotype diversity. Linkage and association analysis of the tagging SNPs showed strong evidence of linkage for all markers with a minimum chi 21 of 7.5 (P=.006) but no association. This suggests that PAX6 may play a role in myopia development, possibly because of genetic variation in an upstream promoter or regulator, although no definite association between PAX6 common variants and myopia was demonstrated in this study.

Genotype-phenotype studies of six novel LPL mutations in Chinese patients with hypertriglyceridemia.

We screened 160 unrelated Chinese hypertriglyceridemic subjects for sequence alterations in the promoter and the 10 exons of the lipoprotein lipase (LPL) gene. We identified one reported mutation (L252R), one common polymorphism (S447X), and six novel mutations: V181I, C283Y, S298R and S338F (found in single individuals), L252V (in two individuals), and A71T (in three individuals). Screening of family members of the above probands revealed a total of 19 mutation carriers, most of whom, though not all, displayed reduced LPL activity and mass when compared to normolipidemic control subjects. In in vitro expression studies, A71T, V181I, L252R, L252V and C283Y decreased the specific activity of the gene product. Interestingly, S298R had no effect on the catalytic activity while S338F increased it. A71T and C283Y reduced the secretion of the mutant proteins significantly while V181I, S298R and S338F had mild effects only. The total LPL mass of all the mutant constructs was reduced compared to that of the wild type construct, probably due to the instabilities of the mutant mRNA or the mutant protein. The heterogeneity in phenotypic effects of these mutations is a likely consequence of their variable effects on proteoglycan binding, conformation and interactions with other secondary genetic or environmental factors.