Abstract
Abstract: :
Purposes: 1. To determine the distribution of mutations at the MYOC gene in different racial/ethnical groups. 2. To determine whether MYOC mutations partially account for the higher prevalence of Primary Open–Angle Glaucoma (POAG) in African Americans. 3. To determine whether the Gln368Stop mutation at MYOC causing POAG is of European origin. Method: MEDLINE was searched to obtain articles reporting MYOC mutations. The overall prevalence and distribution of MYOC mutations in POAG probands from three major human populations were estimated. The overall allele frequency (f) of MYOC mutations in the general population was estimated based on their overall frequency (fG) in POAG probands with the following equation: f = fGp/k where p is the prevalence of POAG in the general population, and k is the average penetrance of MYOC mutations. Results: MYOC mutations are found in 3.75% (156/4157) of Caucasian probands with POAG (including normal tension glaucoma and ocular hypertension), in 3.39% (19/560) of African probands and in 4.86% (39/803) of Asian probands. The rates are similar to the initial estimates by Fingert et al. (Hum Mol Genet, 1999;8:899). Most MYOC mutations are found in a specific racial/ethnical group, a specific country, or a specific region. Since p in African Americans is known to be about 4 times as high as p in Caucasians, f is also about 4 times as high in the African American general population as that of the Caucasian general population. A study showed that the Gln368Stop mutation was found in 1 out of 312 African American POAG probands and in 26 out 1284 Caucasian POAG probands. Several authors have debated that this mutation in the African American POAG proband is of European origin. We provide a mathematical solution to the debate. Since African Americans tend to have an average of 17% Caucasian genetic background, the expected number of African American(s) with POAG carrying the Gln368Stop mutation due to racial admixture is (26/1284)(0.17)(312) = 1.08. This estimate is very close to the actual number in the aforementioned study. Conclusions: 1. Most MYOC mutations are specific to a certain racial/ethnical group, country or region. Thus, they are likely to have occurred after the divergence of major human populations. 2. The higher overall frequency of MYOC mutations in the general African American population is in part responsible for the higher prevalence of POAG in African Americans. 3. The Gln368Stop mutation is exclusively of European origin.
Keywords: clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • genetics • clinical (human) or epidemiologic studies: prevalence/incidence