*7.3.3 MPDZ-NF1B*

The *MPDZ* (multiple PDZ domain crumbs cell polarity complex component) and *NFIB* (nuclear factor I B *NF1B*) genes was found to confer risk to keratoconus based on GWAS on central corneal thickness (CCT) of multi-ethnic Asian populations in Singapore. rs1324183 of *MPDZ-NF1B* gave a significance of *P* = 8.72 × 10<sup>−</sup><sup>8</sup> [113]. The association was replicated inn Australian Caucasian cohort, P = 0.001, OR = 1 [114]. Further examination of the CCT loci in keratoconus patients from two independent Caucasian cohorts also revealed association rs1324183 for keratoconus, *P* = 5.2 × 10<sup>−</sup><sup>6</sup> , OR = 1.33 [79]. In a Han Chinese cohort of 210 patients and 191 controls in northern China, the association was p = 0.005, OR = 3.1 [115]. However, no association was found in a Saudi Arabia study of 108 patients and 300 controls [116]. In contrast, very high risk of rs1324183 to keratoconus, *P* = 4.30 × 10<sup>−</sup><sup>4</sup> OR = 2.22 was shown after genotyping of 133 patients and 367 controls who are Han Chinese in Hong Kong in southern China [117]. In addition, rs1324183 conferred a higher risk to severe keratoconus (OR = 5.10) than the moderate (OR = 2.05) or mild (OR 2.36) form. There was significant correlation between the risk allele A of rs1324183 with the corneal mechanic parameters of anterior Kf, anterior AvgK, posterior Kf and apex pachymetry, indicating association with corneal thickness and curvature. Therefore rs1324183 has been proposed to be a genetic marker for severity and progression of keratoconus [117]. Taken together, there is no evidence of direct causation to keratoconus by *MPDZ-NF1B,* which, however, does pose susceptibility to development and progression of keratoconus.
