01 September 2005
Med Sci Monit 2005; 11(9): LE9-9 :: ID: 428459
Dear Editor, Stroke is a multi-factorial disorder and is a leading causeof morbidity and mortality in the World . Despite extensive efforts and progress in the field, theburden of the disease is rising and is expected to continue to do so in coming years, especially in developingand underdeveloped regions of the World . Identification of novel risk factors, and hence the preventionof disease, has important public health implications. Recently in a previous issue of this journal, Hruskovicovaet al. studied two variants (C282Y) and (H63D) in Hemochromatosis (HFE) gene and investigated their associationwith atherothrombotic cerebral infarction in a case control study design in Slovenia . They failedto show an association with the disease. However there are certain comments and queries that need tobe addressed before ruling out HFE gene's association with the disease. There are ~37 allelic variantsthat have been identified in the HFE gene . The authors of the present study have investigated onlytwo. The bases of the candidate gene based association studies relies on the principle of "Linkage disequilibrium(LD)". According to this principle, single nucleotide polymorphisms (SNP's) in a candidate gene are investigatedto find out if they are linked with an unknown functional variant within the gene. A lack of associationof two out of 37 allelic variants present with in the gene does not permit to conclude that the genecan not be implicated in the pathogenesis of the disease. Moreover, the frequency of the rare alleleof the polymorphisms investigated is too low in their study population. Thus C822Y and H63D are not informativeand not appropriate SNP's to study in Slovenian subjects. The authors should have reported LD betweenC822Y and H63D polymorphims. Based on the LD values, a diplotype analysis should have been done. Manystudies done on complex disorders have found haplotypes or diplotypes explaining the risk of diseasemore than individual SNP's [4,5]. Association studies looking at individual SNP's in association withdisease can have loss of information attributed to biallelic polymorphisms and thus can have inflatedtype-I error attributable to multiple comparisons . This is avoided through analysis of a combinationof sites on specific alleles (phase on chromosomes) in association with the disease. Authors have usedthe term "mutations" for C282Y and H63D. These are polymorphisms and not mutations. Distinction betweenthe two is based on the frequency in the population with mutations having a frequency less than 1%. Analysesof the present study should be repeated before concluding a negative association of HFE gene with atherothromboticcerebral infarction. References: 1.American heart Association: Heart Disease and Stroke Statistics -2003 Update. Dallas, Tex: American Heart Association, 2002 2.World Health Organization (WHO): The atlasof heart disease and stroke. http: //www.who.int/cardiovascular_diseases/resources/atlas/en/ (accessed18 December 2004) 3.Hruskovicova H, Milanez T, Kobal J et al: Hemochromatosis-causing mutations C282Yand H63D are not risk factors for atherothrombotic cerebral infarction. Med Sci Monit. 2005; 11(7): BR248-BR2524.Drysdale CM, McGraw DW, Stack CB et al: Complex promoter and coding region beta 2-adrenergic receptorhaplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA, 2000;97(19): 10483-88 5.Jorde LB: Linkage disequilibrium and the search for complex disease genes. GenomeRes, 2000; 10(10): 1435-44.
Keywords: Brain Ischemia - genetics, genetic variation, Hemochromatosis - genetics, Intracranial Arteriosclerosis - genetics, Intracranial Thrombosis - genetics, Linkage Disequilibrium, Mutation, Risk Factors
01 August 2022 : EditorialEditorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic
Med Sci Monit 2022; 28:e937927
08 Aug 2022 : Clinical ResearchA 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Comp...
Med Sci Monit In Press; DOI: 10.12659/MSM.937331
08 Aug 2022 : Clinical ResearchHemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Progno...
Med Sci Monit In Press; DOI: 10.12659/MSM.937146
05 Aug 2022 : Clinical ResearchA Retrospective Study of 98 Elderly Patients with High-Risk Lateral Femoral Wall Intertrochanteric Hip Frac...
Med Sci Monit In Press; DOI: 10.12659/MSM.936923
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292