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Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population.

Publication ,  Journal Article
Williams, SEI; Whigham, BT; Liu, Y; Carmichael, TR; Qin, X; Schmidt, S; Ramsay, M; Hauser, MA; Allingham, RR
Published in: Mol Vis
April 21, 2010

PURPOSE: To investigate whether variants in the lysyl oxidase-like 1 (LOXL1) gene are associated with exfoliation glaucoma (XFG) and primary open-angle glaucoma (POAG) in an ancestral population from South Africa. METHODS: Black South African subjects with XFG, POAG, and age matched unaffected controls were recruited from the St. John Eye Hospital in Soweto, Johannesburg, South Africa, using standard clinical examination techniques. Fifty individuals were collected for each of the three groups: XFG, POAG, and normal controls. The complete coding region of LOXL1 was sequenced using the PCR-based Sanger method. The allele frequencies of the identified sequence variants were compared between XFG or POAG and controls using Fisher's exact test. RESULTS: A large number of coding variants were identified, including rs1048661 (R141L), rs3825942 (G153D), S159A, S161L, rs41435250 (A320A), rs13329473 (F489F), and T567A. The allele frequencies of both rs3825942 and rs1048661 differed significantly between the XFG and control subjects from South Africa (p=5.2 x 10(-13) and 1.7 x 10(-5), respectively). The G allele for rs1048661 (encoding arginine) was the risk allele which is similar to other populations. The A allele of rs3825942 (encoding aspartic acid) was the risk allele, in sharp contrast to the G allele (encoding glycine) reported in multiple other populations. There was no significant difference in the allele frequencies of coding variants in LOXL1 between POAG and control subjects. CONCLUSIONS: This represents the first genetic association study of LOXL1 in an ancestral African population with XFG. We have confirmed the association between variants of LOXL1 and XFG. To date, the G allele of the major susceptibility variant rs3825942 has consistently been shown in multiple populations to increase the risk of XFG. Surprisingly, we have found a strong association with the opposite allele in the South African population. This suggests that other as yet unknown causal variants of LOXL1 contribute to the genetic risk of XFG.

Duke Scholars

Published In

Mol Vis

EISSN

1090-0535

Publication Date

April 21, 2010

Volume

16

Start / End Page

705 / 712

Location

United States

Related Subject Headings

  • South Africa
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Humans
  • Glaucoma, Open-Angle
  • Genetic Predisposition to Disease
  • Female
  • Exfoliation Syndrome
  • Black People
 

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Williams, S. E. I., Whigham, B. T., Liu, Y., Carmichael, T. R., Qin, X., Schmidt, S., … Allingham, R. R. (2010). Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population. Mol Vis, 16, 705–712.
Williams, Susan E. I., Benjamin T. Whigham, Yutao Liu, Trevor R. Carmichael, Xuejun Qin, Silke Schmidt, Michele Ramsay, Michael A. Hauser, and R Rand Allingham. “Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population.Mol Vis 16 (April 21, 2010): 705–12.
Williams SEI, Whigham BT, Liu Y, Carmichael TR, Qin X, Schmidt S, et al. Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population. Mol Vis. 2010 Apr 21;16:705–12.
Williams, Susan E. I., et al. “Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population.Mol Vis, vol. 16, Apr. 2010, pp. 705–12.
Williams SEI, Whigham BT, Liu Y, Carmichael TR, Qin X, Schmidt S, Ramsay M, Hauser MA, Allingham RR. Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population. Mol Vis. 2010 Apr 21;16:705–712.

Published In

Mol Vis

EISSN

1090-0535

Publication Date

April 21, 2010

Volume

16

Start / End Page

705 / 712

Location

United States

Related Subject Headings

  • South Africa
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Humans
  • Glaucoma, Open-Angle
  • Genetic Predisposition to Disease
  • Female
  • Exfoliation Syndrome
  • Black People