Analysis of Gln223Agr Polymorphism of Leptin Receptor Gene in Type II Diabetic Mellitus Subjects among Malaysians

Abstract

Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05).

Association of LEPR Gln223Arg polymorphism with T2DM: A meta-analysis

“…There was no obvious association between LEPR Gln223Arg polymorphism and T2DM in Asians either (G vs. A, OR = 1.08, 95% CI 0.75 to 1.57, P = 0.68) (Fig. 3) [5][6][7][8][10][11][12][13]15]. …”

“…1), we excluded seven studies which were not according to HWE, and the I 2 was reduced to 47.9% (Fig. 2) [6,7,9,10,14,15]. Sixteen individual studies with 7827 subjects were finally included into the meta-analysis.…”

“…Sixteen individual studies with 7827subjects from 14 publications were finally included into the meta-analysis [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Among those 16 studies, six studies were performed in Caucasian countries, while the other 10 studies were performed in Asians (Table 1).…”

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

“…The LEPR rs1137101 polymorphism (Q223R; Gln223Arg; 668A > G) is an A> G substitution resulting in the exchange of glutamine for arginine at position 668 of LEPR (Figure 1). The presence of this variant was considered as an independent risk factor for T2DM in Malaysian subjects (48). Finns with glucose intolerance and the presence of the GG genotype (Finnish Diabetes Prevention Study) showed a higher risk for T2DM compared to those carrying the A allele.…”

Analysis of selected glutathione S-transferase gene polymorphisms in Malaysian type 2 diabetes mellitus patients with and without cardiovascular disease

“…The International Diabetes Federation (IDF) has predicted that the number of people with diabetes will rise from 285 million in 2010 to 439 million in 2030. In Malaysia, the proportion of known diabetes is estimated to have increased from 6.5 to 9.5%, accompanied by a three-fold enlargement in newly diagnosed cases from 1.8 to 5.4% over the same period (Letchuman et al, 2010;Etemad et al, 2013;Haghvirdizadeh, et al, 2015). Malaysia has different subethnic groups (Hatin et al, 2014).…”