I148M variant of PNPLA3 confer increased risk for nonalcoholic fatty liver disease not only in European population, but also in Chinese population


  • Potential conflict of interest: Nothing to report.

To the Editor:

We read, with great interest, the article by Sookoian et al. reporting on when after having performed a systematic review by a meta-analysis, they found that the I148M variant of PNPLA3 can be used as a risk marker for predicting susceptibility and histological severity of nonalcoholic fatty liver disease (NAFLD).1 Here, we would like to draw attention to our similar studies between rs738409 in PNPLA3 and NAFLD in the Chinese population and that we found significant associations between rs738409 and NAFLD.

Recent genome-wide association studies revealed that the genetic variation, rs738409 (I148M), in PNPLA3 influences NAFLD and plasma levels of liver enzymes.2-4 However, the association of rs738409 with the development and severity of NAFLD in the Chinese population has not yet been reported. We tested the association of histologic NAFLD with the I148M variant of PNPLA3 in 112 patients of NAFLD and 120 matched controls in our department. Our results showed that in the Chinese population, individuals harboring the G allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with the histological fibrosis stage. PNPLA3 may be involved in the progression of fibrosis in NAFLD. Our results showed that the rs738409 G allele in PNPLA3 was significantly associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.03; 95% confidence interval [CI] = 1.98-6.71). After analysis of the association between the G allele of rs738409 in PNPLA3 and the steatosis grade, we found that there was not an association (P > 0.05). Furthermore, we also did not observe any association of this variant with body mass index, triglyceride levels, high- and low-density lipoprotein levels, or diabetes (P > 0.05). Generally, our research results are very similar to Prof. Sookoian's previous report.

In summary, our data highlight three points. First, we show that genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, not only limited to European populations. Second, our research sample size is small and only a single central research, and this did not allow us to get the better results, compared with Prof. Sookoian's report. Third, although the genotypes of different geographic and ethnic factors may have a significant effect on the above results, we still want to say that the I148M variant of PNPLA3 can be used as a risk marker for predicting the susceptibility and histological severity of NAFLD in the Chinese population.

Xiaohua Li Ph.D., M.D.*, Qingchuan Zhao Ph.D. M.D.*, Kaichun Wu Ph.D., M.D.*, Daiming Fan Ph.D., M.D.*, * Xijing Hospital of Digestive Disease, Xi'an, China.