Polymorphic amino acids at codons 9 and 37 of HLA-DQB1 alleles may confer susceptibility to cervical cancer among Chinese women.
Cervical cancer is strongly associated with the infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear HPV infection, some develop persistent infections that may lead to cancer, implying genetic susceptibility factors for malignant progression. To verify whether HLA class II DQB1 polymorphism is related to cervical cancer in Chinese population, HLA-DQB typing was carried out by PCR-SBT for 258 patients with cervical cancer and 284 healthy controls, and the allele frequencies were calculated. In this study, HLA-DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected patients with cervical cancer compared with healthy controls (chi(2) = 31.7452, p < 0.0001; chi(2) = 12.7838, p(c) = 0.0066), but DQB1*050201 allele was significantly lower (chi(2) = 26.2187, p < 0.0001). This result indicates that HLA-DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and DQB1*050201 may contribute to the resistance to the development of cervical cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr at the same two positions, respectively. This finding implies that polymorphic amino acids at the putative antigen binding residues 9 and 37 of HLA-DQB1 alleles may play an important role in the development of cervical cancer.
Wu
Yuping
Y
State Key Laboratory of Biocontrol, Key Laboratory of Genetic Engineering of MOE, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China.
Chen
Yulong
Y
Li
Longyu
L
Cao
Yicheng
Y
Liu
Zehuan
Z
Liu
Benrong
B
Du
Zhengping
Z
Zhang
Yanling
Y
Chen
Shangwu
S
Lin
Zhongqiu
Z
Xu
Anlong
A
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics*; D001224:Aspartic Acid; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003062:Codon / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D052162:Human papillomavirus 16; D006801:Humans; D007532:Isoleucine; D007930:Leucine; D030361:Papillomavirus Infections / Q000150:complications; D010649:Phenylalanine; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D014443:Tyrosine; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics* / Q000821:virology
D000596:Amino Acids; D003062:Codon; D004279:DNA, Viral; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007532:Isoleucine; D001224:Aspartic Acid; D014443:Tyrosine; D010649:Phenylalanine; D007930:Leucine