Abstract
It has been reported that peroxisome proliferator-activated receptor gamma (PPARG) and peroxisome proliferator-activated receptor gamma co-activator 1 (PPARGC1) family (e.g. PPARGC1A and PPARGC1B) are key agents in the development and pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we designed a case-control study and selected PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms to assess the relationship between these polymorphisms and T2DM using the SNPscan method. A total of 502 T2DM patients and 784 non-diabetic controls were enrolled. We found that PPARGC1A rs3736265 G>A polymorphism was correlated with a borderline decreased susceptibility of T2DM. In a subgroup analysis by age, sex, alcohol use, smoking status and body mass index, a significantly decreased risk of T2DM in <65 years and female groups was found. Haplotype comparison analysis indicated that CTTCGGG and CTCTGGG haplotypes with the order of PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms in gene position significantly increased the risk of T2DM. However, CCCCACA haplotype conferred a decreased risk to T2DM. We also found that PPARGC1A rs3736265 A allele decreased the level of fasting plasma glucose (FPG), while increased the level of Triglyceride. In conclusion, Our findings suggest that variants of PPARGC1A rs3736265 G>A polymorphism decrease the level of FPG, improving the expectation of study in individual's prevention strategies to T2DM.
Highlights
Type 2 diabetes mellitus (T2DM) is a most common form of diabetes and is a major public health threat
Our findings suggest that variants of PPARGC1A rs3736265 G>A polymorphism decrease the level of fasting plasma glucose (FPG), improving the expectation of study in individual's prevention strategies to type 2 diabetes mellitus (T2DM)
We identified that PPARGC1A rs3736265 G>A polymorphism was associated with the decreased risk of T2DM
Summary
Type 2 diabetes mellitus (T2DM) is a most common form of diabetes and is a major public health threat. Accumulating evidence suggests that dysfunction of adipose tissue is contributing to the development of IR and T2DM. Obesity represents a situation of increased fat accumulation, whereas lipodystrophy indicates a situation in which the capacity of retaining lipid in adipocytes is impaired, and prevents the accumulation of fat. In these situations, the ability of retaining lipid in adipose tissue is impaired, leading to lipotoxicity and developing peripheral IR [4]. The lipotoxicity, in the β-cell, has been considered to contribute to the etiology and pathology of T2DM [6]
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