A Epidemiological Study Of Primary Angle Closure Glaucoma In ChongQing China And Primary Study Of Primary Angle Closure Glaucoma Susceptibility Gene

Primary angle closure glaucoma(PACG) or angle closure glaucoma(ACG) is retina and optic nerve damage due to a closed anterior angle and increased IOP. The race difference in rate of PACG between white race and yellow race reveals that inherited facts and certain environmental facts are the reason for PACG. Therefore genetics research of PACG is one of important parts in pathogenesis of this disorder.Epidemiological survey in Chinese and Eskimo shows that PACG is called complex genetic diseases, and the heritability value of PACG is 65% in China, 70% of shallow anterior chamber(AC) in Eskimo. Its susceptible facts are shallow AC, narrowing AC angle and short axial length. We known little abaut PACG genetics and its susceptible gene due to the race difference and other reason worldwide, nevertheless, with the development of biology and molecular genetics,it become possible to localizate PACG genes.The purpose of this study include as follows: 1. to furthermore explore phenotypic features of PACG by epidemiological survey. 2.to analyse inherited patterns of PACG susceptibility by collect PACG families. 3. to primarily study chromosome 11 and some of candidate genes on other chromosomes to identify whether or not PACG is related to those chromosome 11 and candidate genes by way of short tandem repeats (STR) linkage analysis.Result428 individu als from 116 families were examined. The affected individuals were older (p<0.01) than the unaffected ones, moreover, the female/male ratio was higher in the affected group than the unaffected group (4.1 vs 1.5). Compared to the unaffected individuals, the affected ones were hyperopic (p<0.01), had shallow peripheral (p<0.01) and central anterior chamber depths, narrow angles (p<0.01), high intraocular pressure (p<0.01), thick lens (p<0.01), and short axial length (p<0.01).Phenotypic features of PACG patients and their family membership such as the depth of anterior chamber and the degree of angle narrow showed consecutively quantitative trait. The quantitative trait of suspect was intermediate phenotypes between unaffected and affected, and did not show statistic difference between affected and unaffected in axial length(p>0.05).The relateive risk of first degree relative was 7.91, and the estimated heritability value of shallow AC was 92.6%±5.87, and the heritability value of female relatives was 115.24%±7.94%.The inherited patterns of shallow AC with males sibs accorded with autosomal recessive heredity, while (P>0.05), while females sibs accorded with autosomal dominant heredity (P>0.05). the genetic pattern of U×A exhibited autosomal dominant inheritance trait, and the genetic pattern of U×U showed neither autosomal recessive heredity nor dominant inheritance traits(P>0.05).75 individuals of 5 chronicPACG families were selected from 114 families and DNA samples were extracted. STR markers within 13 candidate genes or near locus were selected to perform multipoint nonparametric linkage analysis (NPL). LOD score were from -0.17 to 0.96 and p value ranged from 0.02 to 0.8. These results did not support linkange possibility of PACG genes with above candidate genes.16 STR markers, average interval 9.18 cM, on chromosome 11 were scaned and multipoint nonparametric linkage analysis (NPL) were performed. LOD score of 1.16 was obtained at D11S4146(p=0.01),. 1.02 (p=0.02) at D11S902. These results supported linkage with our PACG. pedigrees. LOD score of other STR on chromosome 11 were from -0.17 to 0.96 and p value ranged from 0.02 to 0.8. These results did not support linkange possibility of PACG genes with those locus.Conclusion:Phenotypic features of PACG patients and their family membership such as the depth of anterior chamber and the degree of angle narrow show consecutively quantitative variety. The quantitative trait of suspect was intermediate phenotypes between unaffected and affected.Short axial length and shallow AC may be mostly inherited susceptibile facts. Shallow AC exist more heritability value. First relative of PACG demonistrate may demonstrate more relateive risk to cause shallow AC and there may exist dominant major gene in female relative. The inherited patterns of Shallow AC may be different in gender and mating types.PACG susceptibile gene may not be associated with as below: NNO1,MRCS,PAX6,VMD2,MFRP,NNO2,ROM1,CHX10,MCOP1,MCOPCB2,PITX2,FOXC1,MAF。PACG susceptibile gene may be associated with D11S4146 and D11S902 on chromosome 11.