Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) – a narrative literature review
详细信息 查看全文
- 作者：Vladimir V. Bamm ; Arielle M. Geist ; George Harauz
- 关键词：Comorbidity ; Haptoglobin (Hpt) ; Hemoglobin (Hb) ; Multiple sclerosis (MS) ; Oxidative damage
- 刊名：Metabolic Brain Disease
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：32
- 期：1
- 页码：19-34
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Neurosciences; Neurology; Metabolic Diseases; Biochemistry, general; Oncology;
- 出版者：Springer US
- ISSN：1573-7365
- 卷排序：32
文摘
We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.