Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese.

Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2) = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population.

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes. CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

High-frequency hearing loss among mobile phone users.

The objective of this study is to assess high frequency hearing (above 8 kHz) loss among prolonged mobile phone users is a tertiary Referral Center. Prospective single blinded study. This is the first study that used high-frequency audiometry. The wide usage of mobile phone is so profound that we were unable to find enough non-users as a control group. Therefore we compared the non-dominant ear to the dominant ear using audiometric measurements. The study was a blinded study wherein the audiologist did not know which was the dominant ear. A total of 100 subjects were studied. Of the subjects studied 53% were males and 47% females. Mean age was 27. The left ear was dominant in 63%, 22% were dominant in the right ear and 15% did not have a preference. This study showed that there is significant loss in the dominant ear compared to the non-dominant ear (P < 0.05). Chronic usage mobile phone revealed high frequency hearing loss in the dominant ear (mobile phone used) compared to the non dominant ear.

Polymorphic variants of interleukin-13 R130Q, interleukin-4 T589C, interleukin-4RA I50V, and interleukin-4RA Q576R in allergic rhinitis: A pilot study.

The development of allergic rhinitis is considered to be caused by the complex interactions between genetic predisposition and environmental factors. Polymorphisms in the interleukin (IL)-13/4/4RA pathway have previously been shown to be associated with atopic diseases. The purpose of this study was to determine the association between IL-13 R130Q, IL-4 T589C, IL4 receptor alpha (IL-4RA) I50V, or IL-4RA Q576R polymorphisms and risk of allergic rhinitis in a hospital-based Malaysian population. A case-control pilot study was undertaken and genotyping of these polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism on 54 allergic rhinitis patients and 45 healthy individuals. Polymorphism of IL-13 R130Q showed significant difference in genotype (p = 0.048) and allele (p = 0.002) frequencies in allergic rhinitis when compared with healthy controls. Individuals who were GA heterozygotes (adjusted odds ratio [OR(adj)] = 3.567; 95% CI, 1.211-10.509), and carriers of A allele genotype (OR(adj) = 3.686; 95% CI, 1.300-10.451) and A allele (OR(adj) = 3.071; 95% CI, 1.514-6.232) had an elevated risk of developing allergic rhinitis. The genotype and allele frequencies of IL-4 T589C, IL-4RA I50V, and IL-4RA Q576R polymorphisms were not significantly different between the allergic rhinitis patients and normal healthy individuals and did not show an associated risk with allergic rhinitis. Our findings indicate that polymorphic variant of IL-13 R130Q appears to be associated with increased risk for development of allergic rhinitis in a hospital-based Malaysian population but not IL-4 T589C, IL-4RA I50V, and IL-4RA Q576 polymorphisms. Additional studies using larger sample size are required to confirm our findings and its exact role in allergic rhinitis.