Identification of HLA-C*16:46 allele in a Kuwaiti individual.

One nucleotide substitution in codon 90 of HLA-C*16:02:01 results in a novel allele, HLA-C*16:46.

PLXNA3 Variant rs5945430 is Associated with Severe Clinical Course in Male Multiple Sclerosis Patients.

Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA. rs5945430 genotyping was performed using Taqman genotyping assay. Estradiol levels were determined by enzyme-linked immunosorbent assay. Exome analysis revealed a missense variant (rs5945430) in Plexin A3 (PLXNA3) gene (Xq28) associated with male-specific MS severity. Genotyping of 187 MS patients for rs5945430 confirmed the association of rs5945430G with increased disease severity in MS males (p = 0.013; OR 3.8; 95% CI 1.24-11.7) and disability (p = 0.024). Estradiol levels shown to effect PLXNA3 expression were lower in MS males compared to MS females, and they were lower than control rs5945430G males (p = 0.057), whereas MS females had similar estradiol levels to healthy females reducing the level of expressed PLXNA3 GG in MS females. PLXNA3 rs5945430G is associated with increased disease severity in MS male patients. Estradiol is a possible protective factor against the expression of rs5945430G in MS females.

Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells.

Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high). Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females) for chromosomal copy number aberrations (CNA) and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2-q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46%) exhibited a "feminization" phenomenon in the form of gains of X chromosomes (or an arm of X) and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003) and wild-type BRAF gene status (p-value 0.009). No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.