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Letters |

The GLC1H Glaucoma Locus May Reflect Glaucoma With Elevated Intraocular Pressure—Reply

Mansoor Sarfarazi, PhD; Anne Child, MD, FRCP; Ronald Pitts Crick, FRCS
Arch Ophthalmol. 2007;125(12):1717. doi:10.1001/archopht.125.12.1717-a.
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Adult-onset primary open-angle glaucoma (POAG) is a heterogeneous group of eye conditions that results from mutations in many different genes. One primary risk factor for POAG is elevated IOP. Many different genetic locations have been identified for POAG and IOP independently; however, most of these do not map within close proximity of each other. Recently, we mapped a new POAG locus (GLC1H) on chromosome 2p15-p16.1 The Beaver Dam Eye Study2 also reported evidence for an IOP locus near D2S1777 only by analyses of sibling pairs (P = .007) and not nuclear families (P = .10). Duggal and colleagues have now hypothesized that these 2 genetic loci may code for the same product that controls elevated IOP in the families with POAG linked to the GLC1H locus. While this may be a valid assumption, it is equally likely that these 2 loci code for completely separate products, as there is considerable genetic distance between them and they were identified by different analytical methods. The flanking region of the GLC1H locus (D2S123-D2S2165) was determined by recombinational events in 2 affected subjects.1 However, no such clear boundaries have been established for the IOP locus.2 The lower boundary of the GLC1H locus (D2S2165) maps approximately 16.3 million base pairs (bp) above the IOP locus peak marker of D2S1777. This IOP-linked marker is located more closely (6.7 million bp) to D2S2161, which is our previously published upper boundary for another POAG locus (GLC1B) in the 2cen-q13 region.3 As originally reported by Duggal et al,2 their IOP locus resides more closely to the GLC1B locus and both map in the neighborhood of other genetic loci previously identified for diastolic and systolic blood pressures, linked to D2S2114 and D2S1790, respectively. Although no convincing relationship between systemic arterial blood pressure and IOP has been demonstrated and considerable uncertainty still exists regarding the exact chromosomal location for each of these encoded phenotypes, one may conclude that the most likely chromosomal order is the following: (GLC1H, D2S2165); (D2S2114, diastolic blood pressure); (D2S1777, IOP); (D2S1790, systolic blood pressure); (D2S2161, GLC1B). The IOP locus is still provisional and may not overlap with GLC1H or GLC1B. An independent linkage study of subjects with ocular hypertension that identifies this broad region would help to confirm these genetic loci.


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