Association of neuropeptide Y (NPY), interleukin-1B (IL1B) genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility

Naresh C Laddha; Mitesh Dwivedi; Mohmmad Shoab Mansuri; Mala Singh; Hetanshi H Patel; Nishtha Agarwal; Anish M Shah; Rasheedunnisa Begum

doi:10.1371/journal.pone.0107020

Association of neuropeptide Y (NPY), interleukin-1B (IL1B) genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility

PLoS One. 2014 Sep 15;9(9):e107020. doi: 10.1371/journal.pone.0107020. eCollection 2014.

Authors

Naresh C Laddha¹, Mitesh Dwivedi¹, Mohmmad Shoab Mansuri¹, Mala Singh¹, Hetanshi H Patel¹, Nishtha Agarwal¹, Anish M Shah¹, Rasheedunnisa Begum¹

Affiliation

¹ Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.

Abstract

Background: Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels.

Objectives: Aim of the present study was to explore NPY promoter -399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter -511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo.

Methods: PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B -511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR.

Results: Genotype and allele frequencies for NPY -399T/C, +1128T/C and IL1B -511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. 'TC' haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes.

Conclusion: Our results suggest that NPY -399T/C, +1128T/C and IL1B -511C/T polymorphisms are associated with vitiligo and IL1B -511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients advocates its possible role in autoimmune pathogenesis of vitiligo.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Exons
Female
Gene Frequency
Genetic Predisposition to Disease*
Humans
India
Interleukin-1beta / genetics*
Linkage Disequilibrium
Male
Neuropeptide Y / genetics*
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide*
Promoter Regions, Genetic
RNA, Messenger / metabolism
Sex Factors
Vitiligo / genetics*

Substances

Interleukin-1beta
Neuropeptide Y
RNA, Messenger

Grants and funding

This work was supported by grants to RB (BMS/Adhoc/122/11-2012) ICMR, New Delhi, India; (GSBTM/MD/PROJECTS/SSA/453/2010-2011), GSBTM, Gandhinagar, Gujarat, India and (BT/PR9024/MED/12/332/2007) DBT, New Delhi, India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.