OBJECTIVETo detect single nucleotide polymorphisms (SNPs) of the myocilin (MYOC) gene and to investigate their associations with primary open-angle glaucoma (POAG).

METHODSOne hundred and fifty-seven sporadic patients with POAG and 155 unrelated control subjects without POAG were recruited from staff and visitors to the Prince of Wales Hospital between 1998 and 2000. All study subjects are ethnic Chinese living in Hong Kong. The two populations were matched in frequencies of gender and age. The SNPs of the MYOC gene in POAG patients and control subjects were screened and identified by high throughout conformation sensitive gel electrophoresis and fluorescent labeling automated sequencing. The genotype frequencies of each SNP in the two groups were compared by the Chi2 test or Fisher's exact 2-tailed test.

RESULTSA total of seventeen SNPs were identified from 2172 bp long of the MYOC gene, including all 3 exons and adjacent non-coding regions. The identified SNPs were 1-83G --> A, G12R, P16L, A17S, R46X, R76K, R91X, T123T, D208E, L215P, 730+35A --> G, A260A, I288I, E300K, T353I, Y471C and 1515+73G --> C, respectively. Of these, R91X, E300K and Y471C were found only in POAG patients. A significant difference between POAG patients and control subjects was found in the genotype frequencies of 1515+73G --> C. The frequency of the heterozygote (CG) was 0.6% in POAG patients, significantly less than the 4.5% in control subjects (Fisher's exact 2-tailed test, P=0.036, OR=0.136, 95%CI=0.022-0.828). No significant difference was found between the two populations in genotype frequencies of all other SNPs.

CONCLUSIONThe polymorphisms of the MYOC gene may be related to POAG.

Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Base Sequence ; Case-Control Studies ; Cytoskeletal Proteins ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Eye Proteins ; genetics ; Female ; Gene Frequency ; Genotype ; Glaucoma, Open-Angle ; genetics ; pathology ; Glycoproteins ; genetics ; Humans ; Male ; Middle Aged ; Point Mutation ; Polymorphism, Single Nucleotide

Objectives: Intracranial atherosclerosis, especially the middle cerebral artery (MCA), is the commonestvascular lesion for ischemic stroke the Chinese population. We explored the association of geneticpolymorphism and environmental factors in MCA atherosclerosis in the Chinese population. Methods:One hundred fifty-six ischemic stroke patients with MCA stenosis and 181 well-matched ischemicstroke patients without MCA stenosis were examined by polymerase chain reaction (PCR). ThePCR products were analyzed for lipoprotein lipase (LPL) S447X and paraoxonase1 (PON1) Q192Rpolymorphisms by restriction enzyme digestion. Medical history documentation and investigationof biochemical markers were performed for each subject. Results: Univariate analysis showed thatthe levels of systolic blood pressure (SBP) were higher in the MCA stenosis group. There were nosignificant differences in the genotype and allele frequencies of the LPL S447X and PON1 Q192Rpolymorphism observed between the two groups. But, in the patients above 60 years of age with andwithout MCA stenosis, LPL X carriers have higher level of SBP than the LPL SS genotype carriers.Multivariate logistic regression found that SBP was the significant, independent predictor of thepresence of MCA stenosis patients above 60 years of age (P < 0.001, OR=1.206, 95% confidenceintervals: 1.014-1.032).Conclusions: SBP appears to contribute to the pathogenesis of MCA stenosis among Chinese. Thegene polymorphism of LPL S447X may be associated with atherosclerotic MCA stenosis in Chinesepopulation.