Dataset Information

Replication of the Association Between Keratoconus and Polymorphisms in PNPLA2 and MAML2 in a Han Chinese Population.

ABSTRACT: Keratoconus (KC) is a complex ocular disease that is affected by both genetic and non-genetic triggers. A recent genome-wide association study (GWAS) identified a genome-wide significant locus for KC in the region of PNPLA2 (rs61876744), as well as a suggestive signal in the MAML2 (rs10831500) locus. In order to validate their findings, here we performed a replication study of the Han Chinese population, with 120 sporadic KC cases and 206 gender and age matched control subjects, utilizing the TaqMan SNP genotyping assays. SNP rs10831500, as well as two proxy SNPs for rs61876744, named rs7942159 and rs28633403, were subjected to genotyping. However, we did not find a significant difference (P > 0.05) in all the three genotyped SNPs between KC cases and the controls. A further meta-analysis on four previous cohorts of white patients and this Han Chinese cohort showed a significant genetic heterogeneity within the replicated loci. Thus, the current study suggests that SNP rs61876744 (or its proxy SNPs) and rs10831500 might not be associated with KC susceptibility in this Han Chinese cohort, and a large-scale association analysis focusing on the loci is therefore warranted in further investigations.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7387689 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Replication of the Association Between Keratoconus and Polymorphisms in PNPLA2 and MAML2 in a Han Chinese Population.

Zhang Jing J Li Yue Y Dai Yiqin Y Xu Jianjiang J

Frontiers in genetics 20200722

Keratoconus (KC) is a complex ocular disease that is affected by both genetic and non-genetic triggers. A recent genome-wide association study (GWAS) identified a genome-wide significant locus for KC in the region of PNPLA2 (rs61876744), as well as a suggestive signal in the MAML2 (rs10831500) locus. In order to validate their findings, here we performed a replication study of the Han Chinese population, with 120 sporadic KC cases and 206 gender and age matched control subjects, ut ...[more]

PMID: 32793291

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Project description:Chromosome 6p21-p22.1, spanning the extended major histocompatibility complex (MHC) region, is a highly polymorphic, gene-dense region. It has been identified as a susceptibility locus of schizophrenia in Europeans, Japanese, and Chinese. In our previous two-stage genome-wide association study (GWAS), polymorphisms of zinc finger with KRAB and SCAN domains 4 (ZKSCAN4), nuclear factor-?B-activating protein-like (NKAPL), and piggyBac transposable element derived 1 (PGBD1), localized to chromosome 6p21-p22.1, were strongly associated with schizophrenia. To further investigate the association between polymorphisms at this locus and schizophrenia in the Chinese Han population, we selected eight other single-nucleotide polymorphisms (SNPs) distributed in or near these genes for a case-control association study in an independent sample of 902 cases and 1,091 healthy controls in an attempt to replicate the GWAS results. Four of these eight SNPs (rs12214383, rs1150724, rs3800324, and rs1997660) displayed a nominal difference in allele frequencies between the case and control groups. The association between two of these SNPs and schizophrenia were significant even after Bonferroni correction (rs12000: allele A>G, P = 2.50E-04, odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.12-1.45; rs1150722: allele C>T, P = 4.28E-05, OR = 0.55, 95% CI = 0.41-0.73). Haplotype ATTGACGC, comprising these eight SNPs (rs2235359, rs2185955, rs12214383, rs12000, rs1150724, rs1150722, rs3800324, and rs1997660), was significantly associated with schizophrenia (P = 6.60E-05). We also performed a combined study of this replication sample and the first-stage GWAS sample. The combined study revealed that rs12000 and rs1150722 were still strongly associated with schizophrenia (rs12000: allele G>A, P(combined) = 0.0019, OR = 0.81; rs1150722: allele G>A, P(combined) = 3.00E-04, OR = 0.61). These results support our findings that locus 6p21-p22.1 is significantly associated with schizophrenia in the Chinese Han population and encourage further studies of the functions of these genetic factors.

Project description:AimsDilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc-dependent and calcium-containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population.Methods and resultsA total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865-C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P < 0.05). Besides, rs243865-C allele presented a correlation with the poor prognosis of DCM patients in both dominant (HR = 2.0, 95% confidence interval [CI] = 1.14-3.57, P = 0.017) and additive (HR = 1.85, 95% CI = 1.09-3.13, P = 0.02) model. The statistical significance remained after adjustment for sex, age, hypertension, diabetes, hyperlipidaemia, and smoking status. There were significant differences in left ventricular end-diastolic diameter and left ventricular ejection fraction between rs243865-CC and CT genotypes. Functional analysis indicated that rs243865-C allele increased luciferase activity and the mRNA expression level of MMP2 by facilitating ZNF354C binding.ConclusionsOur study suggested that MMP2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese Han population.

Dataset Information

Replication of the Association Between Keratoconus and Polymorphisms in PNPLA2 and MAML2 in a Han Chinese Population.

Publications

Replication of the Association Between Keratoconus and Polymorphisms in <i>PNPLA2</i> and <i>MAML2</i> in a Han Chinese Population.

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