Molecular genetic analysis of polymorphisms pertaining to the susceptibility to chronic asthma in Egyptian patients

Background: Asthma is a multifactorial inflammatory disorder that might result from the interaction of multiple genes and environmental factors. Several studies of genetic epidemiology have reported the association of cytokine genes with asthma among various populations. However, the results are inconsistent and inconclusive. Objective: To determine the association of cytokine gene polymorphisms with asthma susceptibility in adult Egyptian cases. Subjects: The study included, 50 adult Egyptian asthmatic cases with a mean age of 53.62 ± 14.61 years in addition to 98 healthy individuals as control. For all participants, DNA was isolated from peripheral blood samples and analyzed for TNF-α-308 G > A, IL-10-1082 G > A, IL-6-174 G > C and IL-1Ra VNTR polymorphisms. Results: The comparison between the cases and controls has showed significantly higher frequency of the genotypic polymorphisms: IL-10-1082 AG + GG (dominant mode) (76.1% vs. 91.8%, p = 0.01, OR = 0.3, 95% CI (0.1–0.7), TNF-α-308 GA + AA (dominant mode) (72.0% vs. 93.9%, p = 0.001, OR = 0.17, 95% CI = 0.06–0.47) and IL-1RA VNTR heterozygous genotype A1A2 (90.0% vs. 58.8%, p = 0.0003). Otherwise, compared to controls, cases showed statistically non-significant frequency of genotypes corresponding to IL-6-174 CC + GC vs. GG (dominant mode) (92.0% vs. 94.9%, p = 0.5, OR = 0.6). Conclusions: The IL-10, TNF-α and IL-1Ra allelic variants showed a potent association with chronic asthma among Egyptian cases that might be used as markers with a potential impact on prophylactic and or therapeutic measures for asthma control. Whereas the IL-6-174 allelic variants showed no association with chronic asthma among Egyptian cases

Neonatal Hyperbilirubinemia in infants with <it>G6PD c.563C > T</it><it>Variant</it>

<p>Abstract</p> <p>Background</p> <p>There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. <it>G6PD c.563C > T</it> is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having <it>G6PD c.563C > T.</it></p> <p>Methods</p> <p>This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. <it>G6PDgenotype</it> was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.</p> <p>Results</p> <p><it>G6PD variants c.563C > T</it> and <it>c.131 C > G</it> were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with <it>c.563C > T</it> variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, <it>p</it> < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, <it>p =</it> 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, <it>p =</it> 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.</p> <p>Conclusions</p> <p>We concluded that infants with <it>G6PD c.563C > T</it> variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, <it>G6PD c.563C > T</it> carrying infants had significantly low G6PD activity.</p