Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2019, Vol. 33 ›› Issue (3): 71-78.doi: 10.6040/j.issn.1673-3770.1.2019.006

• Original Article • Previous Articles     Next Articles

Association of vitamin D binding protein geneand CYP27B1 gene polymorphisms with mite-sensitized persistent allergic rhinitis among Han Chinese population

Huiqin TIAN1,2,Zhongfei WU2,Ying LU3,Lei CHENG2,4,5()   

  1. 1. Department of Child Healthcare, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210036, Jiangsu, China
    2. Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu, China
    3. Department of Group Healthcare, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210036, Jiangsu, China
    4. International Centre for Allergy Research, Nanjing Medical University, Nanjing 210029, Jiangsu, China
    5. The Institute of Allergy and Autoimmune Disease, Jiangsu Clinical Medicine Research Institution, Nanjing 210029, Jiangsu, China
  • Received:2019-02-14 Revised:2019-04-18 Online:2019-05-20 Published:2019-08-07
  • Contact: Lei CHENG E-mail:chenglei@jsph.org.cn

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Abstract: Objective

To evaluate whether polymorphisms in the vitamin D binding protein gene (GC) and CYP27B1 gene are associated with mite-sensitized persistent allergic rhinitis(AR) in this population.

Methods

An ongoing hospital-based case-control study consisting of 564 patients with mite-sensitized persistent AR and 583 healthy controls was conducted. Seven single nucleotide polymorphisms (SNPs) in GC and one SNP in CYP27B1 were selected for genotyping.

Results

The genotype and allele frequencies of rs4588，rs7041，rs3733359，rs16847024，rs843008，rs1565572，and rs11939173 in GC as well as rs10877012 in CYP27B1 were not significantly associated with susceptibility to mite-sensitized persistent AR. After stratification analyses, however, there are genotypes in different subgroups of rs16847024 in GC exhibited significantly decreased risk of mite-sensitized persistent AR, compared to wild CC genotype, and they are: CT (adjusted OR=0.62, 95% CI=0.41-0.94) and CT/TT (adjusted OR=0.62，95% CI =0.42-0.90)genotypes in the age subgroup of ≥17 years old, the CT/TT (adjusted OR=0.68，95% CI = 0.48-0.96) genotypes in the male subgroup, the CT (adjusted OR=0.70，95% CI =0.52-0.95) and CT/TT (adjusted OR=0.72，95% CI =0.54-0.97) genotypes in the subgroup of persistent AR without concomitant of asthma, and the CT (adjusted OR=0.70，95% CI =0.52-0.95) and CT/TT (adjusted OR=0.71，95% CI =0.53-0.94) genotypes in the subgroup of lower total IgE level. Analysis of the locus-locus interactions of GC and CYP27B1 revealed one model that involved two SNPs of only GC were statistically significant (P=0.001).

Conclusion

Our data suggest that ≥17 years old, male, no concomitant of asthma, and lower total IgE level may have an impact on the association of SNP rs16847024 in GC of the vitamin D pathway with the risk of mite-sensitized persistent AR in this Chinese population. Two variants of GC may be involved in genetic interactions in the pathogenesis of persistent AR.

Key words: Allergic rhinitis, GC gene, CYP27B1 gene, Single nucleotide polymorphism, Genetic association studies

CLC Number: 

  • R765.2

Table 1

Distribution of selected variables between cases and controls"

变量病例组 (n=564)对照组( n=583)Z/χ2值bP
n%n%
年龄(岁), M (IQR)17.0 (11.0~29.0)19.0 (8.0~29.0)1.1780.239
性别
男37466.337263.80.7910.386
女19033.721136.2
合并哮喘a
是12121.5
否44378.5
血清总IgE (kU/L), M (IQR)248.0 (113.0~543.0)20.5(13.6~59.4)24.236<0.001
血清特异性IgE (kUA/L)， M (IQR)
屋尘螨25.9(5.3~69.2)
粉尘螨21.4(5.5~61.3)

Table 2

Primary information about selected SNPs in GC and CYP27B1"

SNPs位置等位基因a生物学效应MAF b
GC
rs4588外显子C>A错义突变0.278
rs7041外显子T >G错义突变0.289
rs37333595′UTRC>T上游调控序列0.360
rs168470245′NEARC>T上游调控序列0.116
rs8430085′NEART >G上游调控序列0.233
rs15655725′NEARA>C上游调控序列0.453
rs119391735′NEARG>A上游调控序列0.198
CYP27B1
rs108770125′NEART >G上游调控序列0.402

Table 3

Primers and probes for genotype screening by TaqMan allelic discrimination"

SNPs引物（5′-3′）探针
GC
rs4588

F:CAGACTGGCAGAGCGACTAAAA

R:GCAGTTGGAGGCAAAGTCTGA

C: FAM-TGCCACACCCACGG-MGB

A: HEX-TGCCACACCCAAGG-MGB

rs7041

F:CAGACTGGCAGAGCGACTAAAA

R:GCAGTTGGAGGCAAAGTCTGA

G: FAM-AAAATTGCCTGAGGCC-MGB

T: HEX-CAAAATTGCCTGATGC-MGB

rs3733359

F:CTACCAGAGAGTCTTGCAGCACCT

R:GCTTCTGTTTAATAATAATTCTGTGTTGC

A: FAM-CTCTCTCCTATAGGTGAC-MGB

G: HEX-TCTCTCCTGTAGGTGAC-MGB

rs16847024F: AAAAACCAGGAGTGGAACTCATCTG: FAM-ATTCCAATGAATGATCTACCTA-MGB
R: CACTGGGTAAATTCTGTGACTTGTCTA: HEX-TTCCAATAAATGATCTACC-MGB
rs843008F: CAAAACCAATTATAGCAATAAGAACATTAAACAA: FAM-TGAACTAAACAATCCAAG-MGB
R: GAACCATTCAAACATCTTGCTTGTTC: HEX-TGAACTAAACACTCCAAG-MGB
rs1565572F: GGGCATGGTTAGAGGTTGTATATTAACC: FAM-AGCATTGCAGCCTT-MGB
R: GAATCAATTGGCTGGCAAAACA: HEX-TGGAGCATTGAAGCC-MGB
rs11939173

F:CAACCCAGTACCAAAAATAAAGGAA

R:CCGAGGAAGCTGCATCATCT

T: FAM-CCCTGTAGGACCC-MGB

C: HEX-TAACCCTGCAGGACC-MGB

CYP27B1
rs10877012

F:GGGAGTAAGGAGCAGAGAGGTAAA

R:AAGGCTGCAGTGAGTTATGATTGT

C: FAM-TGTGGGAGATTCTTTTA-MGB

A: HEX-TGTGGGAGATTATTT-MGB

Table 4

Genotype and allele frequencies of GC and CYP27B1 polymorphisms among cases and controls"

基因型病例组对照组

OR值

(95%CI)

调整OR值

(95%CI)b,c

n%n%
GC
rs4588n = 561n = 577
CC26447.125844.71.001.00
CA24543.726946.61.12 (0.88~1.43)1.13 (0.88~1.44)
AA529.3508.70.98 (0.64~1.50)0.98 (0.64~1.50)
CA/AA29752.931955.31.10 (0.87~1.39)1.10 (0.87~1.39)
A等位基因a1.04 (0.87~1.24)1.04 (0.87~1.24)
rs7041n = 563n = 583
TT30454.032155.11.001.00
TG21638.422338.30.98 (0.77~1.25)0.98 (0.77~1.25)
GG437.6396.70.86 (0.54~1.36)0.86 (0.54~1.37)
TG/GG25946.026244.90.96 (0.76~1.21)0.96 (0.76~1.21)
G等位基因a0.95 (0.79~1.14)0.95 (0.79~1.15)
rs3733359n = 562n= 576
CC24243.127446.71.001.00
CT25745.723941.50.82 (0.64~1.05)0.82 (0.64~1.05)
TT6311.26310.90.88 (0.60~1.30)0.88 (0.60~1.31)
CT/TT32056.930252.40.83 (0.66~1.05)0.83 (0.66~1.05)
T等位基因a0.90 (0.75~1.07)0.90 (0.75~1.07)
rs16847024n = 564n= 582
CC41473.445578.21.001.00
CT13223.410918.70.75 (0.56~1.00)0.75 (0.56~1.00)
TT183.2183.10.91 (0.47~1.77)0.91 (0.47~1.77)
CT/TT15026.612721.80.77 (0.59~1.01)0.77 (0.59~1.01)
T等位基因a0.81 (0.64~1.03)0.81 (0.64~1.03)
rs843008n= 564n= 582
TT34961.936462.51.001.00
TG19434.418732.10.92 (0.72~1.19)0.92 (0.72~1.18)
GG213.7315.31.42 (0.80~2.51)1.42 (0.80~2.52)
TG/GG21538.121837.50.97 (0.77~1.23)0.97 (0.77~1.23)
G等位基因a1.03 (0.84~1.26)1.03 (0.84~1.26)
rs1565572n= 560n = 574
AA18132.316729.11.001.00
AC26146.628449.51.18 (0.90~1.54)1.18 (0.90~1.54)
CC11821.112321.41.13 (0.81~1.57)1.14 (0.82~1.58)
AC/CC37967.740770.91.16 (0.90~1.50)1.16 (0.91~1.50)
C等位基因a1.08 (0.91~1.27)1.08 (0.91~1.27)
rs11939173n= 564n = 582
GG39469.940970.31.001.00
GA14926.415927.31.03 (0.79~1.34)1.03 (0.79~1.34)
AA213.7142.40.64 (0.32~1.28)0.65 (0.33~1.30)
GA/AA17030.117329.70.98 (0.76~1.26)0.99 (0.76~1.27)
A等位基因a0.94 (0.75~1.17)0.94 (0.76~1.18)
CYP27B1
rs10877012n = 561n = 578
TT23141.226145.21.001.00
TG25345.124742.70.86 (0.67~1.11)0.86 (0.67~1.10)
GG7713.77012.10.81 (0.57~1.16)0.80 (0.56~1.16)
TG/GG33058.831754.80.85 (0.67~1.08)0.85 (0.67~1.07)
G等位基因a0.88 (0.74~1.05)0.88 (0.74~1.05)

Table 5

Stratification analyses of GC rs16847024 polymorphisms in persistent AR subgroups"

SNPs分层变量亚组N (病例/对照) b调整OR (95%CI) c, d
XY eYY eXY/YY e
GC
rs16847024
年龄 (岁)<17278/2800.91(0.61~1.36)1.77(0.52~6.03)0.96(0.65~1.42)
≥17286/3030.62(0.41~0.94)0.60(0.26~1.38)0.62(0.42~0.90)
性别男374/3720.72(0.50~1.02)0.46(0.18~1.19)0.68(0.48~0.96)
女190/2110.83(0.51~1.35)2.00(0.67~5.96)0.94(0.60~1.49)
合并哮喘是121/5830.95(0.58~1.57)1.18(0.34~4.15)0.98(0.61~1.58)
否443/5830.70(0.52~0.95)0.88(0.44~1.79)0.72(0.54~0.97)
总IgE水平a低450/5830.70(0.52~0.95)0.72(0.37~1.41)0.71(0.53~0.94)
高114/5830.95(0.57~1.58)—1.11(0.67~1.82)

Table 6

Multifactor dimensionality reduction models for locus-locus interactions"

模型 a训练样本检验样本交叉一致性P
A40.52750.49076/100.8281
A3 A60.56360.558810/100.0010
A1 A3 A60.58070.50156/100.6320
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