ZFAT gene variant association with multiple sclerosis in the Arabian Gulf population: A genetic basis for gender-associated susceptibility

Abstract

Single nucleotide polymorphisms (SNPs) are useful genetic markers to investigate the onset of multiple sclerosis (MS). A genome wide association study identified 7 SNPs associated with interferon-β therapy response, however, not with MS risk in a Spanish population. To investigate these findings in a different cohort, the 7 SNPs were investigated in an Arabian Gulf population. The SNPs were analyzed in 268 subjects (156 patients and 112 healthy volunteers) from the Arabian Gulf region using restriction fragment length polymorphism-polymerase chain reaction (PCR) and KBioscience Competitive Allele Specific PCR genotyping methods. Associations between the SNPs and MS were investigated using logistic regression. The present study observed, for the first time, that in an Arabian Gulf population, the ZFAT rs733254 polymorphism (T>G) is a gender-specific risk marker for MS. ZFAT was associated with MS in women but not in men. The G variant was highly associated with the risk of MS [odds ratio (OR)=2.38 and 95% confidence interval (CI), 1.45–3.91); P=0.0014]. Whereas variant T was a significantly protective factor [OR=0.420 (95% CI, 0.25–0.69); P=0.0014, recessive model]. The findings of the present study provide a genetic basis for the gender-associated susceptibility to MS. In addition, this MS-associated rs733254 SNP may predict MS onset in females from the Arabian Gulf population.

Multi-level genomic analyses suggest new genetic variants involved in human memory

“…ZFAT can recognize histone H3 acetylation, which is involved in inflammation-mediated epigenetic modulation of memory [30]; another target gene of ZFAT is bromodomain and PHD finger containing 1 [30], which is important for brain development [31] and is associated with schizophrenia [32]. Previous research has found that deficits in ZFAT were associated with autoimmune thyroid disease [33] and a ZFAT variant was associated with multiple sclerosis that sometimes involves memory deficits [34]. So far, its relationship with memory has not been well studied.…”

Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants

“…However, ZFAT is expressed in B and T lymphocytes and has shown to be a critical transcription regulator involved in apoptosis and cell survival (Fujimoto et al, 2009). Bourguiba-Hachemi et al (2016) found that another variant, rs733254 , in ZFAT is a risk marker for multiple sclerosis (MS) in women. Multiple studies have also detected an association between ZFAT and the severity of autoimmune thyroid disease (Inoue et al, 2012; Sakai et al, 2001).…”

Imprinted Genes and Multiple Sclerosis: What Do We Know?

“…It should be mentioned that another study re-established the consistent paternal expression of ZFAT-AS1 in human placenta; the monoallelic expression of the ZFAT gene was also revealed, but random activity of either of the parental alleles [ 122 ]. It was in one of the genetic studies that the polymorphic variant rs733254 in ZFAT gene was associated with RRMS in women, but not in men, in an Arabian Gulf population (odds ratio 2.38 and 95% confidence interval 1.45–3.91; p = 0.0014) [ 123 ]. Genome-wide association study demonstrated the association of this variant with INF-β therapy response in MS patients [ 124 ].…”