Murugesan Devi, Arunachalam Thirunavukkarasu, Ramamurthy Viraragavan, Subramanian Selvi
Department of Biotechnology, PSG College of Technology, Coimbatore - 641 004, India.
Indian J Hum Genet. 2010 May;16(2):72-7. doi: 10.4103/0971-6866.69350.
Candidate gene association studies are very relevant to the area of clinical pharmacology. As information on candidate genes and candidate single nucleotide polymorphisms increases, a number of such candidates can be studied in a population to explore their association with their susceptible disease. One such attractive and popular Single Nucleotide Polymorphism (SNP) candidate for obesity is the gene coding for leptin receptor. The leptin receptor gene (LEPR) polymorphism plays an important role in obesity and type 2 diabetes. But the role of this polymorphism is not yet studied in Indian population. Hence, the study focused to explore the association of leptin receptor polymorphisms (K109R, Q223R and K656N) with obesity and type 2 diabetes in both diabetic and non-diabetic subjects recruited from the local population of Coimbatore.
Genotypic analysis for the three polymorphisms has been made for 300 subjects (150 diabetic and 150 non-diabetic) with the age range of 40-60 years using conventional Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques in a case-control fashion. Allele frequencies were estimated based on the gene count method. Correlation was made with phenotypic variables including body mass index (BMI), waist-to-hip ratio (WHR), insulin and leptin levels for those polymorphisms.
Among the polymorphisms tested in this study, significant association with BMI (P < 0.05), WHR (P < 0.05) leptin (P < 0.001) and insulin (P < 0.0001) was observed for the SNP Q223R, whereas in the case of the other two polymorphisms the association was not statistically significant. The significance value was calculated based on the χ(2) test. The controls are also found to have a higher frequency of homozygous mutants for Q223R and are significantly associated with obesity. These findings support the hypothesis that Q223R polymorphism is associated with obesity. It can be speculated that the controls showing the same allele may develop Type 2 diabetes at a later stage and Q223R can act as a strong marker.
候选基因关联研究与临床药理学领域密切相关。随着候选基因和候选单核苷酸多态性信息的增加，可以在人群中研究许多此类候选基因，以探索它们与易感疾病的关联。肥胖的一个有吸引力且受欢迎的单核苷酸多态性（SNP）候选基因是编码瘦素受体的基因。瘦素受体基因（LEPR）多态性在肥胖和2型糖尿病中起重要作用。但该多态性在印度人群中的作用尚未得到研究。因此，本研究重点探索从哥印拜陀当地人群招募的糖尿病和非糖尿病受试者中，瘦素受体多态性（K109R、Q223R和K656N）与肥胖和2型糖尿病的关联。
采用传统聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）技术，以病例对照的方式对300名年龄在40 - 60岁的受试者（150名糖尿病患者和150名非糖尿病患者）进行了三种多态性的基因分型分析。基于基因计数法估计等位基因频率。对这些多态性与包括体重指数（BMI）、腰臀比（WHR）、胰岛素和瘦素水平在内的表型变量进行相关性分析。
在本研究检测的多态性中，SNP Q223R与BMI（P < 0.05）、WHR（P < 0.05）、瘦素（P < 0.001）和胰岛素（P < 0.
