Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31

Abstract

Three human chromosome loci (1q43, 10p12.31, and 12q21.31) were recently associated with the susceptibility to primary open-angle glaucoma (POAG) in a Japanese population; however, this was not replicated in three subsequent studies using South Indian, Afro-Caribbean, and Chinese populations. To identify genetic markers that are robustly associated across ethnic populations, numerous markers in addition to the six in the three reported loci were examined in this study. A total of 31 single-nucleotide polymorphism (SNP) markers were genotyped for 1115 Korean participants, and many neighboring SNPs were imputed using the Korean HapMap Project genotype data. Each SNP was statistically tested for association with POAG susceptibility by comparisons among 211 POAG patients with 904 unaffected controls. A strong and statistically significant association was found with a previously unreported SNP, rs7098387 (odds ratio, OR ¼ 2.0 (1.4-3.0), P ¼ 0.00038) at the 10p12.31 locus (where 11 SNPs were typed and 38 imputed) in contrast to the reported rs7081455, which was too poorly correlated with newly associated rs7098387 (r 2 ¼ 0.003, D 0 ¼ 0.40) to show association. Additionally, a modest association was observed with the reported rs693421 (OR ¼ 1.4 (1.1-1.7), P ¼ 0.0082) and several other SNPs located within and around ZP4 at the 1q43 locus (10 SNPs typed and 14 imputed). However, no association was observed with the reported rs7961953 SNP or any other SNPs at the 12q21.31 locus, upstream of TMTC2 (10 SNPs typed and 29 imputed). Accordingly, POAG susceptibility association was replicated using rs7098387 (C) rather than rs7081455 (T) at the 10p12.31 locus and additionally with rs693421 (T) at the 1q43 locus.

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study

“…Besides, the functional significance of these SNPs or locus to POAG development remains unknown. In contrast to the findings of Nakano et al [7] and consistent with the findings reported in other population [17,[19][20][21], no significant genotype/allelic effect of these SNPs in POAG was observed in our study. These conflicting results can be ascribed to factors such as differences in sample size, lack of adequate statistical power or differences in the phenotypes of the sample population included in the study.…”

“…The findings were successfully replicated in stage-2 GWA study [7]. However, except for rs693421 (OR = 1.4 (1.1-1.7), p = 0.0082) in Korean [20], Korean (for SNP rs2499601) [21] and very recently in the Han Chinese population [22] have failed to replicate this association between rs693241, rs2499601 and POAG. Besides, the functional significance of these SNPs or locus to POAG development remains unknown.…”

“…The minor allele frequencies observed for these variants in the Saudi population (controls) was comparable to the Oriental population's [7,[19][20][21], but higher than that reported among the Indian [22]. In our study, significant linkage disequilibrium between rs693421 and rs2499601 was found (D' = 0.69) but analysis of distribution differences of the four haplotypes in the POAG cases and controls did not show any significant association with the disease.…”

Association of PAX3 and TMTC2 gene polymorphism with the face morphology change after excision of skin tumors

“…Also, we did not find any difference in the shape of the examined region among TMTC2 genotypes preoperatively, neither postoperatively 27,28 . Besides, like in PAX3 gene, there was no correlation between preoperative and postoperative results, so we could suppose that there was no association between TMTC2 gene and facial morphology in the medial cheek region 29 .…”

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study

“…The findings were successfully replicated in stage-2 GWA study ADDIN EN.CITE [7] . However, except for rs693421 (OR=1.4 (1.1-1.7), p=0.0082) in Korean subjects, subsequent studies in a South Indian ADDIN EN.CITE [17] , Afro-Caribbean ADDIN EN.CITE [18] , Japanese ADDIN EN.CITE [19] , the Hong Kong cohort ADDIN EN.CITE [20] , Korean (for SNP rs2499601) ADDIN EN.CITE [21] and very recently in the Han Chinese population [22] have failed to replicate this association between rs693241, rs2499601 and POAG.…”