Involvement of nuclear factor kappa-B in development of neonatal onset multisystem inflammatory disease

1 Introduction

Neonatal onset multisystem inflammatory disease (NOMID) is a rare inflammatory disease in neonates, and most common causes of morbidity, mortality, and increase economic burden to people (Prieur and Griscelli, 1981; Prieur et al., 1987; Feldmann et al., 2002). The key clinical symptoms among neonates are increase body temperature (fever), development of rashes, hearing loss and psychological impedance. It is characterized by global prevalence of NOMID is approximately 5% of neonates, with higher mortality rates in developing countries China. It is a key reason of death in neonates: over 1 million deaths per year are attributable to NOMID (Aksentijevich et al., 2002; Stojanov and Kastner, 2005; Agostini et al., 2004; Manji et al., 2002). Epidemiological studies have shown, however, that the prevalence of NOMID in neonates is higher than assumed (Agostini et al., 2004). NOMID is a genetic disorder, which is due to the mutation of auto-inflammatory, these results in multisystem inflammatory disease (Prieur and Griscelli, 1981). NOMID is flattering an important public health concern throughout the world and accounts for premature morbidity and mortality (Prieur et al., 1987). The prevalence of NOMID is increasing quickly in recent years in China, accounts for >5% of the overall population (Feldmann et al., 2002). Furthermore, the occurrence of NOMID in Asia is projected to upsurge obviously in subsequent 20 years due to growing occurrence of obesity.

The role of nuclear factor kappa-B (NF-κB) in activating inflammatory mediators, mainly cytokines and inflammatory mediators and it also trigger the range of vital cellular functions. (Wang et al., 2002; O’Connor et al., 2003; Yu et al., 2006; Kanneganti et al., 2006; Grenier et al., 2002; Dowds et al., 2004). The functional role of NF-κB in NOMID was not assessed in Chinese patients. Therefore, this pilot investigation designed to assess whether NF-κB is involved in NOMID in Chinese individuals. The results of present investigation study may encourage conducting large multicentric trials which assess the relationship of NF-κB and PP1 in Chinese patients with NOMID. We hypothesize the relationship between NF-κB and PP1 with NOMID among Chinese neonates. Therefore, the present studye aimed to investigate the relationship of NF-κB and PP1 as one of the possible threat in the cause of NOMID among Chinese neonates.

2 Materials and methods

3 Results

A total of 270 Chinese patients (NOMID: 135 patients and healthy neonates: 135) were enrolled at Maternal and child health hospital of Hubei province. All patients completed study, and data of both the groups (were analyzed using appropriate statistical analysis. Mean (SD) age of NOMID group of neonates was 2.3 (0.5) weeks whereas it was 3.1 (0.7) weeks in healthy subjects. Baseline characteristics in both the groups were comparable (Table 1).

We observed that the participants with GA genotype were vulnerable of NOMID; risk of NOMID was 2 higher in as than participants without GG genotype (p < 0.001). We found that the participants with A allele are also vulnerable for increased risk of NOMID; risk of NOMID was 1.7 times more in these patients than subject with no G allele (p < 0.001). We also notice the involvement of other genotype such as GG and GA among NOMID patients (Table 2). We found the positive relationship of PARPs polymorphisms with NOMID when assessed association between NOMID and PARPs polymorphisms among participants with NOMID. There was no evidence of polymorphism of PARPs than the participants of NOMID with healthy subjects. The participants with C allele were more vulnerable of NOMID; risk of NOMID was 1.5 times greater among participants having allele of C in comparison to subjects with no C allele.

GG and G SNPs of PARPs were found responsible for developing NOMID and the individuals with GA SNPs protect responsible for protecting NOMID. Thus, PARPs involved in NOMID and risk of developing is approx. 1.5 times higher compared to healthy subjects. In our study results shows involvement of TT, CC, GA, GG, AA and CT genotype of PARPs C410T. In our study, threat of developing NOMID was more amongst neonates with del/ins polymorphism. We noted the association of del/ins in developing NOMID (Table 3).

4 Discussion

Identification of potential target for treatment of NOMID is utmost important for effective patient care, this helps in modifying the risk factor associated with NOMID with improve patient care (Dowds et al., 2004). In this study, a total of 135 Chinese subject with neonatal onset multisystem inflammatory disease, and 135 Chinese subject without NOMID were completed study. In our study, GG and G SNPs of PARPs were found responsible for developing NOMID and the individuals with GA SNPs protect responsible for protecting from NOMID. We also observed that the involvement of del/ins (d/i) gene of NFκB1. This shows the role of d/i of NFκB1 in developing NOMID. In our study, threat of developing NOMID was more in neonates with del/ins polymorphism. We noted the association of del/ins in developing NOMID. Thus, NFκB1 and PARPs involved in NOMID and risk of developing is approx. 2 times higher compared to healthy subjects. Subjects with GG genotype were susceptible for developing of NOMID; risk of NOMID was approximately more than 1 times higher than when compared to individuals who had no GG DNA gene. The subject with GG gene remained vulnerable of NOMID; risk of NOMID was 1.5 higher in NOMID subjects with GG gene than subjects without GG gene (p < 0.001). Moreover, the subjects with G allele were vulnerable for greater threat of NOMID; threat of NOMID was 1.3 time more in these patients than subject with no G allele (p < 0.001). We also notice the involvement of other genotype such as AA and GA among NOMID subjects. We found the positive relationship of NFκB1 and PARPs polymorphisms with NOMID when assessed association between NOMID. There was no evidence of polymorphism of NFκB1 and PARPs in NOMID than subjects without NOMID. Subjects with C allele were more vulnerable of NOMID; risk of NOMID was 1.5 times greater among participants having allele of C in comparison to subjects with no C allele (Beg and Baltimore, 1996). Our study result shown that polymorphism of NFκB1 and PARPs is involved in development of NOMID in Chinese individuals. In summary, polymorphism of NFκB1 and PARPs involved in development of NOMID in China. Our study suggested that NFκB1 and PARPs is a potential target for treatment of NOMID; the treatment targeting NFκB1 and PARPs is useful for effective patient care. Our study results encourage large study role of NFκB1 and PARPs polymorphism in NOMID.

5 Conclusion

The results of study shows that polymorphism of NFκB1 and PARPs is involved in development of NOMID among Chinese individuals. Our study suggested that NFκB1 and PARPs is a potential target for treatment of NOMID, the treatment targeting NFκB1 and PARPs is useful. Our study results encourage conducting large study which evaluates role of NFκB1 and PARPs polymorphism in NOMID patients.