Suryadevara Naveen Chandra, Neela Venkata Sanjeev Kumar, Kovvali Srinivas, Pydi Satya Sudheer, Jain Suman, Siva Sai K S R, Valluri Vijaya Lakshmi, Spurgeon Anandaraj M P J
LEPRA India-Blue Peter Public Health & Research Centre, Cherlapally, Hyderabad 501301, India.
Trans R Soc Trop Med Hyg. 2013 Dec;107(12):777-82. doi: 10.1093/trstmh/trt084. Epub 2013 Oct 29.
Polymorphisms in TLR4 may change the function of the protein and alter the efficiency of immune response of host to infection. The high relevance of host gene polymorphisms with outcome of Mycobacterium leprae infection led us to study the genetic association of TLR4 G896A polymorphism in order to identify its risk among contacts of affected leprosy patients.
For case-control study design a total of 628 individuals were recruited; 17 multicase leprosy families which included 32 case-parent trios were considered for family-based study. Genotyping was done using PCR-RFLP method.
In case-control study AA genotype was positively associated while GA genotype was negatively associated with leprosy. In family based transmission disequilibrium test (TDT) analysis allele G was found to be over transmitted to the affected individuals.
Case-control study suggests that homozygous AA genotype may confer susceptibility and heterozygous GA genotype may confer resistance to leprosy, while allele A was observed to increase risk and that of allele G may confer resistance to leprosy. No strong transmission disequilibrium was detected in family-based TDT analysis, possibly due to lower number of trios. In contrast to case-control data allele G was over transmitted to the affected ones in TDT analysis. To conclude, the frequencies of genotypes in household contacts were almost the same as in leprosy patients, suggesting that contacts with AA genotype may be at higher risk of leprosy and may therefore require prophylactic inputs.
Toll样受体4（TLR4）基因多态性可能改变蛋白质功能，影响宿主对感染的免疫应答效率。宿主基因多态性与麻风分枝杆菌感染结局高度相关，促使我们研究TLR4基因G896A多态性的遗传关联，以确定其在麻风患者接触者中的风险。
采用病例对照研究设计，共招募628名个体；选取17个多病例麻风家庭，其中包括32个病例-亲代三联体用于家系研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行基因分型。
在病例对照研究中，AA基因型与麻风呈正相关，而GA基因型与麻风呈负相关。在家系传递不平衡检验（TDT）分析中，发现等位基因G过度传递给患病个体。
病例对照研究表明，纯合子AA基因型可能易患麻风，杂合子GA基因型可能对麻风具有抗性，而等位基因A会增加患病风险，等位基因G可能对麻风具有抗性。在家系TDT分析中未检测到强烈的传递不平衡，可能是由于三联体数量较少。与病例对照数据相反，在TDT分析中等位基因G过度传递给患病个体。总之，家庭接触者的基因型频率与麻风患者几乎相同，这表明AA基因型的接触者患麻风的风险可能更高，因此可能需要预防性干预。
