Abstract: Genetics & dry eye & more

This falls into a class of "high falutin' science" that I have to read twice slowly and will still find that it's way, way, way over my head, BUT I'm including it here because (a) it's potentially relevant to some of the more stubborn+mysterious dry eye cases on DEZ and (b) I found the conclusions really very interesting: That evaporative dry eye and non-sjogrens aqueous deficient dry eye are "different but related" possibly via a genetic factor having to do with a mucin, making them more susceptible to ocular surface damage.

MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients.
Exp Eye Res. 2008 Jun 20. [Epub ahead of print]
Imbert Y, Foulks GN, Brennan MD, Jumblatt MM, John G, Shah HA, Newton C, Pouranfar F, Young WW Jr.

Dry eye syndrome is a collection of common disorders of multifactorial etiology. Although the epidemiology of dry eye has been well studied, reports of genetic patterns that might influence susceptibility to dry eye are few. We reported that the frequency of non-Sjogren's aqueous deficient dry eye patients expressing only the MUC1/A splice variant of the mucin MUC1 may be lower than that of a normal control group [Imbert, Y., Darling, D.S., Jumblatt, M.M., Foulks, G.N., Couzin, E.G., Steele, P.S., Young, W.W., Jr., 2006. MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls. Exp. Eye Res. 83, 493-501]. Also, He et al. [He, Y., Li, X., Bao, Y., Sun, J., Liu, J., 2006. The correlation of polymorphism of estrogen receptor gene to dry eye syndrome in postmenopausal women. Yan. Ke. Xue. Bao. 22, 233-236] reported a difference between Chinese dry eye and control groups in the frequency of a polymorphism in estrogen receptor alpha (ERalpha). In the present study we determined the statistical significance and generality of these observations and tested if the MUC1 splice variant difference between subject groups reflected a difference in the MUC1 variable number of tandem repeat (VNTR) size class. There was a perfect correlation between the MUC1/A or MUC1/B splice variant pattern and the SNP genotype frequency of the SNP (rs4072037) controlling that splicing event. In contrast, western and Southern blotting indicated that MUC1 VNTR size class corresponded to the MUC1 SNP genotype in only 80% of cases. We determined the status of the MUC1 SNP in normal and dry eye populations all of whom were female Caucasians. The MUC1 SNP genotype frequency of the normal control group was statistically different from both the non-Sjogren's aqueous deficient dry eye group with ocular surface staining (P=0.017) and the evaporative dry eye group (P=0.015). We also tested SNP rs2234693 to analyze the polymorphism in the ERalpha gene and found no significant difference in the SNP genotype frequency between the control group and either of the dry eye subtypes. Thus, among Caucasians there is no evidence for an association of the ERalpha gene polymorphism with dry eye syndrome as previously described in a Chinese population. In conclusion, the etiologies of evaporative dry eye and non-Sjogren's aqueous deficient dry eye are known to be different. However, our results suggest that both these subtypes of dry eye disease may share a common mechanism or factor related to MUC1 genotypic differences that affects susceptibility to ocular surface damage. This altered susceptibility may not be related to the MUC1 VNTR size class. Therefore, mechanisms influencing protection of the ocular surface against inflammation and damage in different types of dry eye disease warrant further investigation particularly in relation to MUC1 genotype.