Investigating the influence of LCT rs3754689 polymorphism on inhibitor development in Iranian and Afghan patients with severe hemophilia A

Abstract

Development of alloantibodies against factor VIII (FVIII) in patients with severe hemophilia A is the main complication of FVIII replacement therapy. There are many studies indicating several genetic factors associated with inhibitor development. A recent study showed that there is a correlation between the risk of inhibitor development and LCT rs3754689 polymorphism among Italian hemophilia A patients. The aim of this study was to speculate whether LCT rs3754689 polymorphism is correlated to inhibitor development in Afghan and Iranian patients. In addition, we assessed the association of F8 gene mutations and inhibitor development in Iranian patients. This case–control study was conducted on 33 severe hemophilia A patients with inhibitor and 119 samples without inhibitor. Genotyping was performed by Sanger sequencing, inverse and multiplex PCR. According to the obtained data, we found a significant correlation between LCT rs3754689 polymorphism and the risk of inhibitor development in Afghan patients (observed risk, 0.11; 95% confidence interval, 0.01–0.88; P = 0.012). Among Iranian patients, rs3754689 polymorphism showed no significant association with inhibitor development against FVIII (P > 0.05). However, we found a significant correlation between the risk of inhibitor formation and large deletions and nonsense mutations in F8 gene among Iranian patients (observed risk, 7.25; 95% confidence interval, 1.93–27.18; P = 0.003). Lack of association of rs3754689 polymorphism in Iranian population shows the various effects of genetic markers in different populations. More studies in different ethnicities or larger sample sizes are recommended.

Health‐related quality of life in persons with haemophilia in Afghanistan

“…Although various studies have been conducted on haemophilia patients in Afghanistan 2,14–22 . The present study provides an appropriate description of the status of PWH in Afghanistan for the first time.…”

“…Although various studies have been conducted on haemophilia patients in Afghanistan. 2,[14][15][16][17][18][19][20][21][22] The present study provides an appropriate description of the status of PWH in Afghanistan for the first time. Evaluation of the HRQoL is an important part for assessment of the health status of patients with chronic illness, including haemophilia.…”

Genetic variants at the chromosomal region 2q21.3 underlying inhibitor development in patients with severe haemophilia A

“…ethnicity) of the SIPPET cohort consisting of several populations (mainly Indian, Egyptian and Iranian). Recently, the association of the LCT p.Val219Ile missense variant (rs3754689) to inhibitor development in patients with severe HA has been found in Afghans 36 but not confirmed in Brazilian and Iranian populations 36,37 . Since the allele frequencies of all the identified variants reported in the 1000 Genome project are similar in the European and the South Asian populations but are markedly different in the Italian population (Table 1), a replication study performed in an independent cohort of Italian patients could be suitable to overcome the problem of poor reproducibility of genotyping results.…”