Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation.
The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction-complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 +/- 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P =.009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an alpha value of.05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (chi(2) = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy (n = 4) or during pregnancy (n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its prevention and treatment and help protect against thrombi in other vascular beds.
Cholesterol Center, Cincinnati, OH 45229, USA. glueckch@healthall.com
Charles J
CJ
Glueck
Ping
P
Wang
Howard
H
Bell
Venkat
V
Rangaraj
Naila
N
Goldenberg
D000368:Aged; D001778:Blood Coagulation Disorders / Q000201:enzymology / Q000235:genetics*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D018917:Optic Neuropathy, Ischemic / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012171:Retinal Vessels / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors
D004247:DNA; D042965:Methylenetetrahydrofolate Reductase (NADPH2)