The association of type 2 diabetes with the P12A polymorphism of the peroxisome proliferator–activated receptor gene (PPAR-γ2) has been established in several populations (1). However, no studies have thus far been reported for Arab populations. While many variants have been identified in this gene, the most prevalent and best studied is the P12A polymorphism. There is considerable interpopulation variance in the incidence of the risk allele (P12). This ranges in frequency 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 (2).
We utilized a case-control study to test association of the PPAR-γ P12A variant with type 2 diabetes in an Arab (Saudi) population for the first time. Genotyping was performed using a molecular beacon–based real-time PCR assay developed in our laboratory and validated in >100 samples by direct sequencing. The study population consisted of 1,137 individuals of Saudi ancestry with type 2 diabetes as defined by World Health Organization criteria and ranging in age from 20 to 85 years. The control group consisted of 219 individuals of Saudi ancestry >60 years old (range 60–92 years) having a fasting blood glucose <7 mmol/l. The control group was restricted to normoglycemic individuals >60 years of age to minimize inclusion of those likely to develop type 2 diabetes later in life. In addition, P12A genotyping was also performed on a random sample of 727 Saudi neonatal bloodspots to ascertain P12A allele frequencies in an unbiased sample.
Data analysis was first performed for an age- and sex-matched cohort in which the type 2 diabetic cases (n = 118) and control subjects (n = 219) were >60 years old. The male-to-female ratios of these case and control subjects were 1.40 and 1.43, respectively. The P, or risk allele, frequency was 0.974 and 0.968 in type 2 diabetic and control subjects, respectively, and was not statistically significant (P = 0.633). However, given the very high incidence of the P allele in this population, the study size was extremely underpowered. No age-related differences in P12A allele frequencies were observed. Demonstration of statistical significance or lack thereof in the Saudi population, at a 95% CI or better, is impractical, as this would require case and control populations where n is >175,000. The high incidence of the P allele in the Saudi population was confirmed by the neonatal sample set in which frequency of this allele was found to be 0.957. Clearly the risk allele frequency of the Saudi population is comparable to the Japanese, Chinese, and African Americans and is among the highest observed to date.
