Genetic Polymorphism Analysis Of Toll Like Receptor4 Gene In Chinese Han And 54 Minority Nationalities

Background:Human TLR4 (Toll-like receptor 4) response to identify pathogenic microorganisms PAMPs in the natural immune and induce the expression of CD80, it plays an important role in natural immune and adaptive immune, and the study of TLR4 gene single nucleotide polymorphisms (SNPs) becomes a research hotspot. Many reports focus on two missense mutations, Asp299Gly and Thr399Ile, of TLR4, and differences in the frequencies of these two polymorphisms amongst different ethnic groups worldwide have been described hitherto. But few study related to 3'UTR of this gene. Especially, there is no data of TLR4 SNPs in Chinese minority nationalities yet., The aim of the present study is to investigate the frequencies of 3 TLR4 polymorphisms, Asp299Gly , Thr399Ile and rs11536889 located in 3'UTR, in totally 54 Chinese minority nationality and Chinese Han population for the first time. It could be helpful to understand the genetic relationship and ancestral origins of different ethnic groups of China.Material and Methods:The polymorphisms of TLR4 gene 3 SNPs (Asp299Gly, Thr399Ile and rs11536889) in Chinese Han population and Chinese minority nationality was investigated using polymerase chain reaction (PCR)-restriction fragment length polymerase (RFLP) and direct sequencing techniques. The results were made statistical and biological analyzing by SPSS11.5 and Haploview4.1.Results and Conclusions:1. The most rich polymorphisms of Asp299Gly or Thr399Ile were detected form minorities living in northwest of China. There are 10 nationalities, Uighur, Tajik, Tatar, Kazakh, Uzbek, Russians, Kirgiz, Sala, Yugur and Bonan, show Asp299Gly polymorphisms with an average frequency of 0.042. And 7 nationalities, Uighur, Tajik, Tatar, Kazakh, Uzbek, Russians and Xibe, show Thr399Ile polymorphisms with an average frequency of 0.018. The frequency of these two genetic variations are similar with that of Caucasian population, which might be attributed to gene exchange and population migration between the northwest ethnic Chinese minorities and Caucasian populations.2. The polymorphisms of Asp299Gly or Thr399Ile were also detected from minorities residing in Yunnan province. Two nationalities, Deang and Primi, represent the Asp299Gly polymorphism of 0.063 and 0.01 frequency. Three nationalities, Deang, Jingpo and Dai, bear Thr399Ile polymorphism of 0.062, 0.031 and 0.01. No polymorphisms of these two sites were detected from other 22 minorities in this province With 26 ethnic groups in total, Yunnan has the highest number of ethnic groups amongst all Chinese. The complex origion and migration history of minorities in this region might result in the different polymorphisms display of TLR4 Asp299Gly and Thr399Ile3. There is no polymorphism of Asp299Gly and Thr399Ile detected in Han populations and minorities distributing in northeast of China is consistent with the conclusion that East-Asia populations have poor polymorphisms of these two sites.4. The incomplete linkage disequilibrium between Asp299Gly and Thr399Ile were detected in Uighur, Tajik, Tatar, Kazakh, Uzbek, Russians and Deang, that is some different from the cosegregation state amongst these two mutations in Caucasian populations.5. All nationalities carry the rs11536889 polymorphisms except Tatar. The She shows the highest mutation frequency of 0.471, while Primi bears the lowest mutation frequency of 0.02. Take Chang Jiang as the boundary, rs11536889 shows significant polymorphisms differences between the North population and the South population of China, which with the average mutation frequency of 0.11 and 0.276 respectively.