ARID5B, IKZF1, GATA3, CEBPE, and CDKN2A germline polymorphisms and predisposition to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric cancer. Germline single nucleotide polymorphisms (SNPs), including ARID5B (rs10821936 T/C), IKZF1 (rs4132601 T/G), GATA3 (rs3824662 G/T), CEBPE (rs2239633 G/A), and CDKN2A (rs3731217 A/C) have been linked to pediatric ALL in different populations. Hitherto, no previous studies have tested the relationship between these SNPs and pediatric ALL in Gaza strip. Therefore, we investigated the association between these polymorphisms and the occurrence of childhood ALL in this part of Palestine. This case-control study recruited 100 healthy controls and 78 ALL patients. Allele-specific PCR (AS-PCR) technique was used for SNPs genotyping. Relevant statistical tests were used and the multifactor dimensionality reduction (MDR) approach was applied in the analysis of gene-gene interactions. Minor alleles of ARID5B rs10821936 T/C (p = 0.007) and IKZF1 rs4132601 T/G (p = 0.045) were significantly higher in ALL patients. The homozygous (TT) genotype of GATA3 rs3824662 G/T (p = 0.038), (CC) of ARID5B rs10821936 T/C (p = 0.008), and (AC and CC) genotypes of CDKN2A rs3731217 A/C (p < 0.0001) were significantly higher in ALL cases. On MDR analysis, the best model for ALL risk was the five-factor model combination of the examined SNPs (CVC = 10/10; TBA = 0.632; p < 0.0001). This work demonstrates the association of ARID5B rs10821936 T/C, IKZF1 rs4132601 T/G, GATA3 rs3824662 G/T, and CDKN2A rs3731217 A/C polymorphisms with increased risk of pediatric ALL among a patient cohort from Gaza Strip. Further studies with a larger sample size are needed in order to confirm these findings and test the value of these SNPs in prognosis and treatment sensitivity.

Relationship between ApoE gene polymorphism and coronary heart disease in Gaza Strip.

BACKGROUND: Apolipoprotein E (ApoE) plays a role in the regulation of lipid metabolism in humans. ApoE, a 229-amino-acid polypeptide, is classified into three major isoforms (E2, E3, and E4) according to the differences in amino acids at positions 112 and 158. In the normal population, ApoE3 isoform is the most prevalent, and ApoE2 or E4 is frequently associated with hyperlipoproteinemia. The objective of this work was to investigate the relationship between ApoE gene polymorphism and coronary heart disease (CHD) in Gaza Strip and investigate the association between serum lipid levels and CHD. MATERIAL AND METHODS: The study population consisted of 137 subjects including 69 CHD cases (45 male, 24 female) and 68 healthy subjects (33 male and 35 female). RESULTS: The ApoE3/E3 genotype was the most common in the control and the CHD groups. ApoE2/E3 and ApoE3/E4 were the next most common genotypes. The frequencies of ApoE alleles in the CHD subjects were 0.826 for E3, 0.137 for E4, and 0.0362 for E2. These frequencies are comparable to those found in the control group which were 0.875 for the E3, 0.073 for E4, and 0.0515 for E2. No statistically significant differences in ApoE genotypes were found between the patients and the control groups. Moreover, there was no significant difference between the mean of triglyceride (TG) and HDL levels among different ApoE genotypes. However, there was a significant difference in the mean of LDL and ApoE genotypes where the mean of LDL was 218.17 mg/dl in ApoE4, 149.67 mg/dl in ApoE2, and 184.52 mg/dl in ApoE3. A significant difference was also evident between the mean of LDL levels in the CHD and the control group where the mean of LDL was 126 mg/dl in CHD and 111.47 mg/dl in the control group. Our study indicated that there was no significant difference between the mean of cholesterol and TG levels of the CHD and the control groups. CONCLUSIONS: To our knowledge, this is the first study in Gaza Strip investigating the relation between ApoE genotypes and CHD. Further investigations are needed to link other genetic factors to CHD.

Screening for Y-chromosome microdeletions in a population of infertile males in the Gaza Strip.

Infertility is an extraordinary public health problem in the Arab world, as it affects about 15% of couples seeking children. The male partner is responsible for infertility in approximately half of these cases. Classic microdeletions of the Y-chromosome involving the azoospermia factor (AZF) regions are known to be associated with spermatogenic impairment, and non-obstructive azoospermia must be differentiated on the basis of endocrine evaluation and testicular biopsy. Partial AZFc deletions remain controversial because there is no clear agreement regarding their role in spermatogenic failure. In the current study, 50 fertile males (controls) and 125 patients with primary idiopathic male infertility were studied in order to describe the frequency of Y-chromosome mirodeletions among male infertility patients in the Gaza Strip-Palestine area. No Y chromosome classical microdeletions could be detected in any of the 125 infertile men, suggesting that ethnic factors, genetic background, and Y chromosome haplogroups are key factors in such deletions. On the other hand, six gr/gr and one b1/b3 AZFc partial deletions were detected in the infertile population. The gr/gr deletion was also noted in relatives of four of the six patients with this deletion, and in one of the fertile controls. In conclusion, our study shows that the incidence of Y-chromosome microdeletions in our population is rare; these data suggest that other genetic, epigenetic, nutritional and/or local factors are responsible for impairments in semen parameters observed in this Gazan population. We further hypothesise that the gr/gr deletion is not associated with male infertility, at least in this sub-group.

Natural killer cell lymphoma/leukemia with homozygous loss of p27/kip1.

We describe a case of natural killer (NK) cell lymphoma/leukemia with only an interstitial deletion in the short arm of chromosome 12 as the primary event. Fluorescence in situ hybridization revealed that the ETV6 locus (12p13) and subtelomeric sequences are not deleted in the process. The p27/kip1 locus (12p12-13), a candidate tumor suppressor gene, was deleted on the abnormal chromosome. Sequence analysis detected an adenine nucleotide deletion in the third codon of exon 1 leading to frameshift and premature termination at codon 41 of the retained copy of p27/kip1. To the best of our knowledge, this is the first report in literature on a NK cell lymphoma/leukemia with complete loss of p27/kip1.