In Egypt, a little attention has been paid to define the possible genetic liability for IPF. In this study, we searched for the correlation between the (T) allele of the mucin gene subtype B and the risk for ILD. The minor allele (T) was detected in 6 individuals as heterozygous genotype (GT) and in only 2 individuals as homozygous genotype (TT) among the 40 normal individuals, indicating that the T-allele polymorphism percentage was approximately 20% in our sample. Other studies conducted on other Caucasian populations demonstrated that the T-allele percentage was 10.81%, 11.74%, 10%, and 9.1% in the French, Italian, UK, and in the US Caucasian population, respectively [17,18,19].
Our results revealed that the minor-allele (T) polymorphism in the IPF patients (group I) was present in 21 patients as heterozygous G/T genotype and in 5 patients as homozygous T/T genotype, denoting that the T-allele frequency was approximately 61.9% among the IPF patients. Also, the presence of the allele (T) polymorphism in the other ILD patients (group II) was detected in 15 patients as the heterozygous G/T genotype and in 2 patients as homozygous T/T genotype, showing that the T-allele polymorphism was approximately 36.1% among the other ILD patients. The (T) allele frequency was significantly higher among the IPF patients (group I) in relation to the other two groups (P value < 0.001). Hence, our data support a strong correlation between the T-allele of the mucin gene subtype B and the occurrence of IPF, in the Egyptian patients which is the same to the studies in the Caucasian population in Europe and the USA [15, 17, 22].
A Chinese study concluded that the frequency of the (T) allele in normal Chinese persons was approximately 0.66%, which was lower than that described in the Caucasian population and our study. However, the frequencies of the T allele were significantly higher among their IPF and ILD patients than healthy Chinese controls, 3.33% and 2.22% respectively .
In this study, the T-allele of the MUC5B in other ILD patients was not significantly different compared to the control subjects. A finding that suggests the absence of any relation between MUC5B polymorphism and lung fibrosis in the context of autoimmune conditions, either NSIP or UIP.
It is clear that IPF is higher in older age groups. In our study, the mean age of IPF patients was (47.8 ± 8.8 years). Our findings were similarly in line to a study conducted by Kaddah et al., which included 102 IPF patients from Egypt; the mean age of their patients was 50 ± 13 years . Also, our results goes with that of an Egyptian study that was conducted in Upper Egypt and showed that the mean age of their IPF patients was 44 ± 12 years .
In multiple studies, IPF appears to have sex predilection being more common in men; some suppose that this difference may be related to smoking patterns rather than sex as a risk for IPF [26, 27]. This is against our results in which most of the IPF patients (group I) were females (59.5%). All of them were non-smokers and housewives. Only 33.3% and 36.2% of the female IPF and other ILD patients gave history of raising birds respectively. There were 17 male IPF patients (40.5%); 35.7% gave history of cigarette smoking compared to 10 male IPF patients (21.3%); 10.6% gave history of cigarette smoking. Interestingly, our results matched that of a study conducted by Sherbini et al., which included 134 IPF patients from Saudi Arabia; 56% of their patients were females and 44% were males; smoking was more evident as 36% of IPF patients were smokers .
In this study, the frequency of the T allele of MUC5B among male individuals (25%) was lower than female individuals (75%) in the control group, but it was statistically insignificant (P = 1.000). Moreover, we investigated the possibility of the affection of a function of MUC5B gene by gender among our IPF patients. The results did not detect any significance in the T allele percentage between both female (82.4%) and male ILD (17.6%) patients and their normal pair controls as well as between female (50%) and male (50%) IPF patients and matched controls. Borie et al. reported that the T allele risk was not affected by sex in Caucasians . They considered that the mucin 5B subtype could have an independent effect on the liability to IPF. However, in the Chinese study, the (T) allele percent was considerably lower in the Chinese population and significantly differed between Chinese males and females. The T allele was significantly higher among male IPF patients compared with the corresponding healthy controls (3.75% versus 0.37%, P = 0.001), denoting the possible correlation between T allele of the mucin gene subtype B and IPF .
Detection of risk factors for IPF is a critical issue in order to take steps towards preventive strategies, early diagnosis, and novel therapies. Smoking is one of risk factors for IPF. Additionally, smoking appears as a co-factor for increasing MUC5B expression. Smoking could augment the level of MUC5B expressed by alveolar macrophages at the long term [29,30,31,32,33,34]. Recently, the smoking rates were high among both European males and females [35, 36]. Among our IPF patients, 15 males were smokers compared to only 5 males of other ILD group with positive statistical significance (P value 0.006). Also, the number of the IPF smoker patients was the highest compared to the other 2 groups (P value 0.016). None of our female patients were smokers. This highlighted that the minor-allele (T) in male IPF smoker patients was high with P value = 0.014. Our results suggest that smoking could accelerate the process of IPF in patients with the mucin gene 5B variant. However, due to the lack of smoking among our Egyptian female patients, we failed to detect an association between the MUC5B polymorphism and female patients with IPF in this study.
One of the suggested risk factors for IPF is bird raising in Egypt. A multicenter hospital-based case control study from 2010 to 2011 performed in Egypt found strong occupational and exposure associations as woodworking and chemical/petrochemical industry for men and raising birds and farming for women and risk for IPF . Our results showed that there were 14 subjects raising birds among the IPF patients (group I) compared to 17 subjects raising birds among the other ILD patients (group II) with no statistical significance between the 2 groups (P value = 0.779). The percentage of the minor allele (T) is 4 (15.4%) among IPF raising birds patients (group I) while in the other ILD patient raising birds (group II), the configuration of the minor-allele (T) was present in 6 (35.3%) cases. Our results showed that, despite there were 16 IPF female patients with GG phenotype for the MUC5B, the fact that 10 (62.5%) of those patients were raising birds may had an influence and played an essential role for development of IPF in those patients. The environmental risk factors as raising birds may be a potential cause for development of IPF even with GG phenotype for the MUC5B subjects. However, multicentric researches are required to focus on the possibility of relation between the mucin 5B gene and the bird-raising exposure in the pathogenesis of IPF.
In this study, the mucin gene subtype B polymorphism was not associated with disease severity as evidenced by FVC values and oxygen saturation values of our patients in both groups. However, in the Chinese study performed by Jiang et al., the MUC5B is associated with IPF severity .
This study has limitations as the relatively small numbers in each group and high cost of laboratory kits. Future researches in Egypt using larger patient cohorts are required to confirm the findings of this study.