|Year : 2013 | Volume
| Issue : 1 | Page : 39-42
Frequency distribution of hemoglobin variants among Yorubas in Ibadan, south western Nigeria: A pilot study
Thomas Nubila1, Ernest Okem Ukaejiofo1, Nkoyo Imelda Nubila2, Rahman Azeez1
1 Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Enugu State, Nigeria
2 Department of Pharmacology and Therapeutics, Faculty of Medical Sciences, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Enugu State, Nigeria
|Date of Web Publication||30-Dec-2013|
Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Enugu State
Source of Support: None, Conflict of Interest: None
Background: Inherited disorders of hemoglobin are the most common gene disorders worldwide. The objective of this study is to determine the frequency distribution of hemoglobin variants among the Yorubas residing in Ibadan. Materials and Methods: Five hundred and thirty one subjects comprising 184 males and 347 females, of age 1-70 years, were enrolled in the study. Ethical approval was obtained from the Ethical Committee of the University College Hospital and a duly signed informed consent was obtained from each subject. Two milliliters of venous blood was aseptically collected from each participant for the determination of hemoglobin genotype, using the standard hematology method. Results: Hemoglobin HbAA recorded the highest frequency distribution (65.3%). This was followed by hemoglobin variant HbAS (24.1%), abnormal hemoglobin variant HbSS (5.5%), HbAC (4%), and HbSC (1.1%), (P > 0.05). The female subjects revealed higher frequency distributions of AA, AS, SS, and SC, while the male demonstrated higher frequencies in AC and SC only. Conclusion: It can be concluded that the Yoruba indigenes residing in Ibadan have a high frequency distribution of HbAA and a future reduction in the HbSS disease in the populace is possible.
Keywords: Frequency, hemoglobin, Ibadan, variants, Yorubas
|How to cite this article:|
Nubila T, Ukaejiofo EO, Nubila NI, Azeez R. Frequency distribution of hemoglobin variants among Yorubas in Ibadan, south western Nigeria: A pilot study. Niger J Exp Clin Biosci 2013;1:39-42
|How to cite this URL:|
Nubila T, Ukaejiofo EO, Nubila NI, Azeez R. Frequency distribution of hemoglobin variants among Yorubas in Ibadan, south western Nigeria: A pilot study. Niger J Exp Clin Biosci [serial online] 2013 [cited 2020 Feb 25];1:39-42. Available from: http://www.njecbonline.org/text.asp?2013/1/1/39/123962
| Introduction|| |
Hemoglobin has a quaternary structure characteristic of many multi-subunit globular proteins.  Most of the amino acids in hemoglobin form alpha helices, connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein; causing attractions within the molecule, folding each polypeptide chain into a specific shape.  The hemoglobin's quaternary structure comes from its four subunits, in a roughly tetrahedral arrangement. 
The hemoglobin molecule consists of four globular protein subunits. Each subunit is made up of a protein chain that is tightly associated with a non-protein heme group. Each protein chain is arranged in a set of alpha-helix structural segments, linked together in a globin fold arrangement.  This folding pattern contains a pocket that strongly binds the heme group.
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates,  with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates. Hemoglobin in the blood transports oxygen from the respiratory organs to the rest of the body, where it releases the oxygen to metabolize the nutrients to provide energy to power the functions of the organism, and collects the resultant carbon dioxide, mainly to bring it back to the respiratory organs to be dispensed from the organism. Hemoglobin has an oxygen binding capacity of 1.34 ml of O 2 per gram of hemoglobin,  which increases the total blood oxygen capacity 70-fold compared to the dissolved oxygen in the blood. The mammalian hemoglobin molecule can bind up to four oxygen molecules. 
Hemoglobinopathy is a type of genetic defect that results in an abnormal structure of the globin chains in the hemoglobin molecule.  They are also inherited single-gene abnormalities; which in most cases are inherited as autosomal co-dominant traits.  One of the most severe hemoglobinopathies is the sickle cell disease. It is estimated that 70% of the World's population are carriers, with 60% of the total and 70% of the pathological being in Africa. Hemoglobinopathies are more common in the ethnic population from Africa, the Mediterrenean basin, and South East Asia. 
In addition, hemoglobinopathies also involve structural abnormalities in the globin proteins themselves.  However, some other mutations are referred to as hemoglobin variants, while another group, called the porphyrias, is characterized by errors in the metabolic pathways of heme synthesis. A separate set of diseases called thalassemias involve under production of normal and sometimes abnormal hemoglobin, through problems and mutations in the globulin gene regulation.  However, the two conditions (hemoglobinopathies and thalassemias) may overlap, as some conditions that cause abnormalities in the globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.
Several studies on the prevalence of hemoglobin variants in different Nigerian populations have been conducted with conflicting results. ,,,,, In addition, there has been little to no recent scientific literature on the prevalence of hemoglobin variants among the Yorubas in Ibadan, despite an increase in the (1) awareness of sickle cell anemia, (2) premarital test by most churches, (3) genetic counseling by government and non-government organizations (NGO), (4) prenatal diagnosis of hemoglobinopathies, and (5) health and social facilities. We seek to re-evaluate the frequency distribution of hemoglobin variants among the Yorubas in Ibadan, South Western Nigeria.
| Materials and Methods|| |
This study was conducted at the University College Hospital (UCH) Ibadan, Oyo State South-Western Nigeria. The study area was the Ibadan metropolis, an ancient city, which comprises of Egbeda, Ido, Oluyole, Lagelu, Akinyele, Ibadan Southwest, Ibadan North East, and Ona Ara Local Government areas of the Oyo State. Ibadan has a population of approximately 3,800,000. 
Subject Selection and Sample Collection
Five hundred and thirty one subjects comprising 184 males and 347 females, who were either attending or admitted to the UCH, Ibadan, participated in this study between December 2011 and February, 2012. They were all Yorubas residents, in Ibadan. The age ranged between 1 and 70 years.
Ethical approval was obtained from the Ethics Committee of the UCH, Ibadan. Duly signed informed consent was obtained from each participant or relation. Information on age, sex, and local government of origin, were appropriately recorded. All procedures on subject handling were in accordance with the HELSINKI Declaration of 1975, as revised in 2000.  Two milliliters of venous blood were aseptically collected from each participant into a tripotassium Ethylenediaminetetraacetic acid (K 3 EDTA) anticoagulant bottle and mixed immediately by gentle inversion. The hemoglobin genotype were determined using the cellulose acetate electrophoresis technique, as described by Dacie and Lewis.  All samples collected were analyzed within 24 hours.
This was done using the Statistical Package for Social Sciences (SPSS) computer software. The chi-square test was employed for comparison and P < 0.05 was regarded as being statistically significant. The Hardy-Weinberg law  was used to calculate the predicted distribution of the hemoglobin genotype in the population.
| Results|| |
Among the total population studied, the hemoglobin genotype AA (HbAA) recorded the highest frequency distribution (65.3%). This was followed by hemoglobin variant HbAS (24.1%), hemoglobin variant HbSS (5.5%), and HbAC (1.1%), P > 0.05, chi 2 = 8.970, df = 4. In addition, the female subjects revealed higher frequency distributions in AA, AS, SS, and SC, while the male demonstrated higher frequencies in AC and SC only [Table 1].
Only HbAS and HbCC recorded higher predicted values than the measured value, although, it was not statistically significant (P > 0.05) [Table 2].
|Table 2: Percentage distribution of measured and predicted hemoglobin variants in the population|
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According to the Hardy-Weinberg formula, when the percentage genotypes of the subjects were expressed as a proportion of 1.0, the gene frequencies were Hb AA = 65.3, HbAS = 24.1, HbSS = 5.5, and HbAC = 1.10 [Table 2],
Where the gene frequency (%) = % frequency of homozygous + (½ × % freq. of heterozygous)
Hb A = 65.3 + 12.05 + 2 + 0 = 79.35
Hb S = 12.05 + 5.5 + 0 + 0.55 = 18.1
Hb C =0 + 0 + 2 = + 0.55 = 2.55
Given that a, s, and c, represent HbA, HbS, and HbC, respectively, and further expressing them as a proportion of 1 gives HbA = a = 0.653, HbS = s = 0.181, and HbC = c = 0.0255. Using the Hardy-Weinberg law, the distribution of hemoglobin variants of the newborn in the population (i.e., predicted value) would be obtained with the formula:
(a + s + c) 2 = a 2 + 2as + s 2 + 2ac + 2sc + c 2 = 1.0
| Discussion|| |
Sickle cell disease (SCD) or disorder is a collective name for a group of hereditary blood conditions characterized by the formation of sickle cells. The most prevalent in the people of African descent is sickle cell anemia, which is caused by a single amino acid substitution [Glu-Val] at the sixth position of the β-chain of hemoglobin S (HbS), leading to a significant reduction in the solubility of the deoxy-form of HbS, causing polymer formation inside the red blood corpuscles.  The disease is almost endemic and the highest mortality rate is among children from one to ten years in some regions of the world.
From the result of this study, HbAA recorded the highest frequency distribution (65.3%) in the total number of subjects studied (531). This could be attributed to increasing awareness of the disease among the general population by both governmental and non-governmental organizations, appropriate counseling and testing before marriage, and prenatal diagnosis of sickle cell disease. This result was in agreement with other recent studies by Adeyemo et al.,  Egesie et al.,  Erhabor et al., and Pennap et al.,  and was within the normal African reference range (30-40%). However, their interpretation should be re-examined, as it was most likely that the frequency distribution of HbAA would increase with increased awareness and genetic counseling of sickle cell disease and other hemoglobinopathies. Also, most of the previous reports investigated a smaller population (150-200) and these were mainly University students, who were likely to be healthy and possessed normal hemoglobin, HbAA, in order to withstand the usual academic stress, as opposed to their HbSS sickle cell counterparts, who hardly survived before they could gain admission into a higher institution. 
In addition, the female subjects had higher hemoglobin variant frequency distributions in AA, AS, SS, and SC, while the male had higher frequencies in AC and SC only. There was no association between sex and hemoglobin variant distribution. This could be attributable to the fact that hemoglobinopathies are not sex-linked. The result of this study agreed with that of an earlier report by Pennap et al., who suggested that gender had no effect on the incidence of hemoglobin variants. However, the higher number of female subjects studied in this study could have probably contributed to the higher hemoglobin variant frequency distribution, as also the cultural/religious belief, as the Yorubas are more prone to a polygamous lifestyle.
As explained earlier, the high frequency of HbSS in this study could be attributed to, (1) the high number of subjects studied, (2) subject selection, (3) cultural practice and lifestyle of the population studied, (4) absence or underutilization of the genetic counseling facilities in the place, prenatal diagnosis of the disease, and so on. However, this was contrary to a lower, but non-statistically significant (P > 0.05) predicted value, indicating that the prevalence of hemoglobin SS-sickle cell anemia would decrease. From the result of this study, it can be concluded that the Yoruba indigenes residing in Ibadan have a high frequency distribution of HbSS and a future reduction in the disease in this populace is possible.
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[Table 1], [Table 2]