The Peroxisome Proliferator–Activated Receptor-γ2 P12A Polymorphism and Type 2 Diabetes in an Arab Population

Abstract

its use (1). Metformin has been associated with lactic acidosis. Although metforminassociated lactic acidosis (MALA) is rare, it is fatal in approximately half of all cases. MALA is precipitated by clinical conditions that cause substantial tissue hypoperfusion and hypoxia and thus are identified as precautions and contraindications to its use in package labeling (1,2). Four studies have previously found that metformin is commonly prescribed, despite risk factors, with a range of 24.5-54% in outpatients and 64-73% in inpatients (3,5-7). The purpose of our study was to determine the frequency of inappropriate prescribing of metformin to patients with precautions or contraindications at an academic health center and secondarily to compare the findings with previously published studies. This retrospective study was approved by the institutional review board of the University of Michigan. We performed a chart review where 100 inpatients and 103 outpatients were randomly selected from 300 patients who received metformin between January and June of 2003. Patients' medical records were used to collect demographic data, clinical characteristics, laboratory parameters, and information about contraindications and precautionary conditions. Risk factors for MALA were identified through ICD-9 codes in the clinical data repository, laboratory tests, and medical notes. A power analysis estimated that a sample size of 78 patients in each group was sufficient to detect a 20% difference in the frequency of inappropriate prescribing compared with the frequency (73%) reported by Holstein et al. (␣ ϭ 0.05, ␤ ϭ 0.8) (3). A sample size of 100 patients per group was selected for simplicity. Frequencies of inappropriate prescribing were compared with literaturereported rates using Fisher's exact test (4). Inpatient results were compared with those of Calabrese et al. (5). Outpatient results were compared with those of Emslie-Smith et al. (6).

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population

“…The conclusions are not uniform. Positive (10,27,41,42), null (14,26,37), and negative associations (10) between the Pro/ Ala genotype and obesity measures have been reported for various populations. However, in our study we did not observe any effect of the interaction between the variant and BMI on the variables examined.…”

PPARγ2Pro12Ala Polymorphism and Human Health

“…Resistance to the risk of diabetes has been found in Ala12 allele carriers compared to Pro12 allele carriers in ethnic populations as diverse as Japanese [114–116], Korean [117], Iranians [118], Scotts [119], Danish [120], Finns [121], French [122], Spanish [106], and American Caucasians [123, 124]. On the other hand, Ala12 allele has also shown to be functional leading to a predisposition to T2D in populations of Germans [125, 126], Finns [127], Italians [128], Dutch [129], US Caucasians [130], French Caucasians [81], British/Irish Caucasians [131], Asian Indians (Sikh) [132], Parkateje Indians [133], and Arabians [134]. Again, no such effect of Ala12 on the risk of type 2 diabetes can be observed in such diverse populations of Italians [135], Tunisians [136], Qatarians [137], Polish [138], and non-Hispanic and Hispanic white women [139].…”

Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population

“…These associations were also observed in most of the Arab populations of MENA region like Tunisians, Lebanese, [ 14 – 18 ], Iranian [ 19 , 20 ], and North Africans [ 21 ]. Although these polymorphisms were established as risk factor for T2DM in most of the populations studied so far, however, some of the studied polymorphisms seem not to be a major contributor to T2DM susceptibility in the Saudi and Emirati Arab populations [ 22 – 24 ]. There is considerable inter-population variation in the frequency of the risk allele ( Pro12 ) which ranges from a high of 0.96–0.98 in populations including the Japanese, Chinese, and African Americans to 0.91 in Pima Indians and a low of 0.81 in the Finnish population [ 25 ].…”