BACKGROUNDPrimary open-angle glaucoma (POAG) is characterized by optic nerve damage and consists of a group of genetically heterogeneous disorders. This study was to investigate the associations of genetic and environmental factors with POAG in a hospital-based Chinese population.

METHODSThirty-two adult onset POAG patients and 96 age-sex matched control subjects were studied by multivariable logistic regression analysis for the relationships between POAG and its risk factors including family history, diabetes, hypertension, cardiovascular diseases, cigarette smoking, alcohol consumption and polymorphisms of the myocilin and the optineurin genes.

RESULTSUnivariate analysis showed that POAG was related to family history, cardiovascular disease, alcohol consumption and a myocilin sequence alteration (T353I) (P < 0.04). Multivariable logistic regression analysis confirmed that POAG was significantly associated with family history (OR = 20.2), hypertension (OR = 3.58), cigarette smoking (OR = 10.8), alcohol consumption (OR = 0.028) and T353I (OR = 6.03, all P < 0.05).

CONCLUSIONSFamily history, hypertension, cigarette smoking and T353I in the myocilin gene are risk factors for POAG. Alcohol consumption, however, has a protective effect.

Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking ; adverse effects ; Cytoskeletal Proteins ; Eye Proteins ; genetics ; Female ; Glaucoma, Open-Angle ; etiology ; genetics ; Glycoproteins ; genetics ; Humans ; Hypertension ; complications ; Logistic Models ; Male ; Middle Aged ; Risk Factors ; Smoking ; adverse effects

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