Dinucleotide (AC)n Repeat Polymorphism (rs36213840) in the Promoter Region of IL18R1 Gene and Genetic Susceptibility to Severe Malaria

Background: Cytokines are key regulator s of human immune response to malaria but polymorphisms within the regulatory or coding regions of their genes may lead to differences in expression levels which may consequently influence disease susceptibility. In this study, we characterized an adeninecytosine (AC)n dinucleotide repeat polymorphism (rs36213840) at the promoter region of the Interleukin 18 Receptor 1 (IL18R1) gene and investigated its association with severe malaria. Methods: We utilised the case-control study design to enrol a total of 207 children including 87 severe malaria cases and 120 asymptomatic controls. DNA was extracted from blood spot on filter paper using QIAamp® DNA Mini Kit (Qiagen, Hilden, Germany). Genotyping for dinucleotide repeat polymorphisms was done by PCR and capillary electrophoresis of sequenced products on ABI PRISM® 3100 DNA sequencer (PE Applied Biosystems). Results: The genotype frequencies of the dinucleotide repeats differed significantly between the two groups (χ2 = 8.69, P=0.026). We found a significantly higher frequency of the 14bp (AC)7 allele in severe malaria patients than in asymptomatic controls (odds ratio 1.945, 95% CI: 1.23 – 3.09, P = 0.005) while the frequency of the 16bp (AC)8 allele was significant higher in the asymptomatic controls than in severe cases (odds ratio 0.431, 95% CI: 0.244 – 0.761, P = 0.004). Conclusion: Results of this suggest that the 14bp (AC)7 dinucleotide repeats might be a genetic risk factor for susceptibility to severe malaria while the 16bp (AC)8 dinucleotide repeats might be a protective factor against severe malaria

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT ) locus

Calcitonin (CT), a calcium-regulating hormone,lowers the calcium level in serum by inhibiting bone resorption.Because CT may play a role in the pathogenesis ofosteoporosis, genetic variations in or adjacent to the CTgene may be associated with variations in bone mineraldensity (BMD). The present study examined the correlationbetween a dinucleotide (cytosine-adenine; CA) repeatpolymorphism at the CT locus and BMD in 311 Japanesepostmenopausal women (mean age, 64.1 years). Seven alleleswere present in this population; each allele contained 10,11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated therespective genotypes A10, A11, A16, A17, A18, A19, andA20. The A10 and A17 alleles were the predominant allelesin the population studied. Z scores (a parameter representingdeviation from the age-specific weight-adjusted averageBMD) were compared between individuals that possessedone or two alleles of each genotype and those that did notpossess the allele. Subjects who possessed one or two A10alleles had lower BMD Z scores than those who did not(lumbar 2–4 BMD Z score; 20.148 6 1.23 vs 0.182 6 1.54;P 5 0.04). No significant relationships were observedbetween allelic status and background data or biochemicalparameters. The significant association observed betweenBMD and genetic variations at the CT locus implies thatpolymorphism at this locus may be a useful marker for thegenetic study of osteoporosis.