BackgroundUncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population.MethodsA total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene.ResultsObesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account.ConclusionsWe have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population.

A study on the prevalence of coronary heart disease (CHD) and its risk factors in Ceningan Island was conducted. The prevalence of CHD was 11.5%. Older age (odds ratio, OR, 27.0), underweight (OR, 3.6), systolic hypertension (OR, 4.6), high total cholesterol (OR, 5.9), and high low-density lipoprotein cholesterol (OR, 3.1) were risk factors for a history of myocardial infarction (MI). By logistic regression analysis, only age (B=3.937) and underweight (B=1.275) consistently appeared to be risk factors for MI. The prevalence of CHD in the population was comparatively high.

Type 2 diabetes mellitus (T2DM) is still a global health problem. Current T2DM treatments are limited to curing the symptoms and have not been able to restore insulin sensitivity in insulin-sensitive tissues that have become resistant. In the past decade, some studies have shown the significant role of a chaperone family, heat shock protein 70 (HSP70), in insulin resistance pathogenesis that leads to T2DM. HSP70 is a cytoprotective molecular chaperone that functions in protein folding and degradation. In general, studies have shown that decreased concentration of HSP70 is able to induce inflammation process through JNK activation, inhibit fatty acid oxidation by mitochondria through mitophagy decrease and mitochondrial biogenesis, as well as activate SREBP-1c, one of the lipogenic gene transcription factors in ER stress. The overall molecular pathways are potentially leading to insulin resistance and T2DM. Increased expression of HSP70 in brain tissues is able to improve insulin sensitivity and glycemic control specifically. HSP70 modulation-targeting strategies (including long-term physical exercise, hot tub therapy (HTT), and administration of alfalfa-derived HSP70 (aHSP70)) in subjects with insulin resistance are proven to have therapeutic and preventive potency that are promising in T2DM management.

Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (-1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (-1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.