Life is not possible without blood. Blood loss is not just accidental; there are those related to blood abnormalities, among which hemophilia which is a constitutional hemorrhagic disease, is seriously at risk of fatal hemorrhage, linked to the X chromosome and transmitted genetically according to a recessive mode [1]. This genetic anomaly is characterized by a deficiency of factor VIII (haemophilia A) with an occurrence rate of around 1 in 5000 male births and factor IX (haemophilia B) with an occurrence rate of around 1 in 30,000 male births [2]. Its prevalence is little known in Africa for several reasons: The rarity of the disease, the high cost of treating it, the insufficient number of haematology specialists and the lack of adequate laboratories for the biological diagnosis of this disease [3], for example, a recent study carried out in Madagascar showed only a total of 19 hemophilia [4]. However, it has been established that haemophilia is a ubiquitous condition that affects one in 10,000 to 12,000 births, without distinction of race or geographical region [5]. In Cameroon, the World Federation of Hemophilia reported that in 2016, 176 out of 23,439,189 people had hemophilia [6]. The first cases detected and treated in Cameroon date back to the 1970s, in the haematology department of the Yaoundé Hospital and University Centre (CHUY) [7]. The clinical manifestations associated with haemophilia correspond to uncontrolled internal haemorrhagic episodes [8]. The severity and frequency of these manifestations depend directly on the level of circulating plasma factor VIII or factor FIX [9]. The numerous bleeding episodes that individuals with severe hemophilia experience can lead to long-term disability. Recurrent joint bleedings can result in severe arthropathy, muscle atrophy, pseudo-tumors, and lead to chronic pain and impaired mobility that often requires surgery and arthroplasty to improve joint function. Haemophilia A and haemophilia B display similar clinical characteristics; however, several studies have reported possible differences [10]. The possible different clinical evolution of haemophilia B was initially suggested in 1959 by Quick [11]. He observed that haemophilia B, even in its most severe form, can be less incapacitating and disabling than haemophilia A. In some studies, severe haemophilia B has been defined with a factor IX < 2% that could contribute to a less severe bleeding tendency compared to haemophilia A, usually defined with a factor VIII < 1% [12] [13] [14]. It has also been reported that haemophilia B patients have a less severe arthropathy [15] and less hospital admission rate [12] than haemophilia A patients. Hemophilia is diagnosed in the laboratory by coagulation tests and screening and testing the inhibitor development, now the most serious complication in hemophilia, is vital for any comprehensive hemophilia treatment program to be able to provide medical treatment and eradication of inhibitors [16]; however, most centres around the world do not have inhibitor testing capacities. Genetic assessment of hemophilia is important to define disease biology, establish diagnosis in difficult cases, predict risk of inhibitor development, and provide a prenatal diagnosis if desired. Wherever possible, genotype analysis should be offered to all patients with hemophilia [17]. The mainstay of treatment for hemophilia involves replacing the missing blood coagulation factor VIII in people with hemophilia and factor IX when bleeding episodes occur (on-demand treatment) or by scheduled infusions several times per week (prophylaxis treatment). Both plasma-derived (pd) and recombinant clotting factor concentrates are suitable for these different strategies of hemophilia management [18]. Nowadays, many studies are being carried out on polymorphisms within the genes coding for factors VIII and IX [19] [20] [21]. Both factor VIII and IX genes contain two types of polymorphisms. Polymorphisms have a scientific interest of their own and are useful in fields as varied as forensics [22] [23] and the study of human evolution [24]. They have clinical relevance in the context of hereditary disorders in that they can be used to detect a defective (or normal) patient through an affected family. Linkage studies have been used to study carrier status and prenatal diagnosis in hemophilia A and B [25]. The factor VIII gene contains several SNPs, many of which fall into the subcategory of restriction fragment length polymorphisms (RFLPs), such as the alleles of BclI and HindIII RFLPs, which have very high frequencies in Black Americans compared to other ethnic groups [26]. Depending on the nature of the mutation that causes the disease, the affected clotting factor may be completely absent from the patient's body, or present but in a dysfunctional form [27]. The human factor IX gene contains several SNPs, most of which fall incidentally into the RFLP subcategory, such as the MseI SNP located at −698, so involvement has been described in cases of severe haemophilia [27]. These differences result in varying degrees of severity of the disease. Advances in molecular genetic technologies are becoming routinely integrated into many genetic diagnostic laboratories. Full F8 or F9 gene screening is performed by polymerase chain reaction (PCR) and Sanger sequencing, or next-generation sequencing [28] [29]. Use of these techniques is evolving and increasing internationally. The approach and use of a specific technique depend on the available technical expertise and resources. That’s why we used the RFLP-PCR method that was available to us It was noted that very few studies on polymorphisms of factor VIII and IX genes have been carried out in Africa, particularly in Cameroon. Hence our interest in determining HindIII and MseI in the Biomolecular Profile of Hemophilia in Cameroon: A Primer Study.

The vast majority of haemophilia patients registered at CHUY until December 2018 were not able to participate in the study. Indeed, several authors have been confronted with this problem. This was the case of Driscoll et al. who worked on 29 men including 13 black and 16 white men in 1988 in the United States [25]. Similarly, Lalloz et al. worked on 25 men [32]. In Africa, Diop et al. worked on 54 men with haemophilia. Finally, in Cameroon, different authors have worked

P: P value; n %: proportions in percentage.

on samples generally ranging from 9 to 40 patients. According to Doncarli et al., this difficulty is due to the irregular follow-up of minor forms of haemophilia in treatment centres [33]. In our context, the reason for this small sample could be due on the one hand to the refusal of some patients to participate in the study, on the other hand to the fact that many of them did not reside in the city of Yaoundé where we conducted the study, and also that some of the patients registered had already died at the time of the study. Three-quarters of our sample had haemophilia type A. This corroborates the global statistics. For example, Doncarli et al. in one of the largest cohort studies in 2005 in France found a trend almost identical to our sample [33]. Furthermore, the vast majority of patients were suffering from severe forms as opposed to the much less common mild forms. On this subject, the literature consulted is not consensual. Some authors such as Antonarakis et al. [34] in an international study in 1995 found that mild haemophilia is the most widespread. Diop et al. in 2003 found that the moderate form was the most widespread [2]. Doncarli et al. 2005 in France [33] and Tagny et al. in 2014 in Cameroon [7] found a trend rather similar to ours, with the severe form more widespread, followed by the moderate form and finally the mild form. Almost all of our patients had HindIII SNP, which corroborates the results of Husain et al. in 2009 and Moharrami et al. 2015 [35] [36]. Indeed, these two authors found a very high frequency of HindIII SNP (>75%) in black Americans, low in whites and Chinese and absent in Japanese. This study does not show any significant link between the HindIII SNP of the F8 gene and the complications of haemophilia. However, the relationship between the HindIII SNP of the F8 gene and the severity of haemophilia showed a highly significant association (P = 0.000). In addition, patients with severe haemophilia all had the F8 gene HindIII SNP. This SNP would therefore be strongly linked to the severity of haemophilia. In this respect, very few studies in the world have mentioned this aspect. In our study, the MseI SNP was only slightly found. This aligns with the results of Winship et al. in 1993 and Bowen 2002 among Caucasians and Thais [21] [27]. Our study reveals no significant link between the MseI SNP of the F9 gene and the severity or complications of haemophilia.

Our study revealed that the frequency of HindIII SNP of the F8 gene was higher in the participants and so there is a possible association of HindIII SNP of the F8 gene with the severity and complications of haemophilia, however, we found no significant association of MseI SNP of the F9 gene with the severity and complications of haemophilia.

We gratefully acknowledge the Cameroonian Hemophilia Society. The Laboratory of Public Health Research Biotechnology (LAPHER-BIOTECH); and the Laboratory of Hematology at the University Teaching Hospital of Yaounde.

WFM, CT, JPKC, CNE, contributed to the design of the study. CNE, SEE, JPKC, coordinated the study. CNE, AC, VM supervised the enrolment of patients and sample collection. JPKC, CNE, CTF, performed the molecular analysis. SEE, Analyzed data. CNE, SEE, JPKC, writing up the manuscript. All authors contributed in the revision of the manuscript and approved the final version of the manuscript prior to submission.

The authors declare no conflicts of interest regarding the publication of this paper.

Eyebe, N.A.C., Eyebe, E.S., Chedjou, K.J.P., Fomboh, T.C., Chendjou, A., Mabopda, V., Tayou, C. and Mbacham, F.W. (2022) HindIII and MseI in the Biomolecular Profile of Hemophilia in Cameroon: A Primer Study. Journal of Biosciences and Medicines, 10, 8-19. https://doi.org/10.4236/jbm.2022.106002