New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8.

Central corneal thickness (CCT) is a highly heritable trait, which has been proposed to influence disorders of the anterior segment of the eye. A genome-wide association study (GWAS) of CCT was performed in 2269 individuals from three Croatian and one Scottish population. In the discovery set (1445 individuals), two genome-wide significant associations were identified for single nucleotide polymorphisms rs12447690 (ß = 0.23 SD, P = 4.4 × 10(-9)) and rs1536482 (ß = 0.22 SD, P = 7.1 × 10(-8)) for which the closest candidate genes (although ≥90 kb away) were zinc finger 469 (ZNF469) on 16q24.2 and collagen 5 alpha 1 (COL5A1) on 9q34.2, respectively. Only the ZNF469 association was confirmed in our replication set (824 individuals, P = 8.0 × 10(-4)) but COL5A1 remained a suggestive association in the combined sample (ß = 0.16 SD, P = 1.1 × 10(-6)). Following a larger meta-analysis including recently published CCT GWAS summary data, COL5A1 was genome-wide significant (ß = 0.13 SD, P = 5.1 × 10(-8)), together with two additional novel loci. The second new locus (defined by rs1034200) was 5 kb from the AVGR8 gene, encoding a putative transcription factor with typical ZNF and KRAB domains, in chromosomal region 13q12.11 (ß = 0.14 SD, P = 3.5 × 10(-9)). The third new locus (rs6496932), on 15q25.3 (ß = 0.13, P = 1.4 × 10(-8)), was within a wide linkage disequilibrium block extending into the 5' end of the AKAP13 gene, encoding a scaffold protein concerned with signal transduction from the cell surface. These associations offer mechanistic insights into the regulation of CCT and offer new candidate genes for susceptibility to common disorders in which CCT has been implicated, including primary open-angle glaucoma and keratoconus.

No association between histamine N-methyltransferase functional polymorphism Thr105Ile and Alzheimer's disease.

Several abnormalities, including lower histamine levels in brain, elevated serum histamine and degeneration of histaminergic neurons in tuberomammillary nucleus, were described in the histaminergic system of patients with Alzheimer's disease (AD). Histamine is a central neurotransmitter with several functions in brain including regulation of memory, cognition, locomotion, and is degraded in part by histamine N-methyltransferase (HNMT). A common Thr105Ile polymorphism within HNMT gene results in decreased enzyme activity. The Thr105Ile polymorphism was associated with Parkinson's disease, essential tremor, attention-deficit hyperactivity disorder (ADHD), asthma and alcoholism, thus we tested possible association of HNMT functional polymorphism with AD. We have tested 256 AD cases and 1190 healthy controls of Croatian origin. Thr105Ile polymorphism was determined by TaqMan RT-PCR Genotyping Assay and EcoRV digestion. Prevalence of functional HNMT polymorphism among all tested groups was similar and frequency of less active Ile105 variant was 11.5% among AD patients and 13.4% for healthy controls (p=0.26, X(2)=1.25). Our results indicate lack of the association of HNMT Thr105Ile functional polymorphism with Alzheimer's disease.