We read with much interest the report of Venkatesh et al. [1] concerning the mitochondrial genome ATPase6 gene mutations associated with primary ovarian insufficiency (POI). Their study catalogued ATPase6 gene nucleotide polymorphisms in idiopathic cases of POI. These authors found that nucleotide changes in the ATPase6 gene were higher in the POI patients compared to a control group. They also suggested that two non-synonymous mutations, in the ATPase6 gene, 8684C[T and 9094C[T were significantly (P \ 0.005) associated with POI cases. We suggest however, that their results and conclusions are significantly weaker than they seem because they failed to examine their data thoroughly. Mitochondrial genome substitutions present in a homoplasmic fashion (haplotypes) are commonly associated in genetic lineages (mtDNA haplogroups). We reexamined the data of Venkatesh et al. [1] employing mtDNA phylogenetic tree analysis. We found that of their six mutations in the ATPase6 gene five were attributable to distinct south Asian, West Eurasian and East Asian haplogroups. Mutations 8679A[G, 8865G[A, and 9094C[T are a characteristic motif of south Asian haplogroups M39, M4b2 and U2b1, respectively [2–4]. The mutations 8684C[T and 9123G[A are defining markers for the west Eurasian haplogroups U7 and H4 [3, 5]; this mutation also occurs in the East Asian haplogroups M8a and B4a [6]. While the west Eurasian H4 and the East Asian M8a haplogroups are almost nonexistent in India, the U7 haplogroup is present in 10–15% of the population in north India [7]. Therefore, it is apparent that the substitution 8684C[T and 9123G[A scored in the POI cases actually are common mutations indicating that their carriers belong to the haplogroups U7 and B4a. The mutation 9064G[A is also a commonly occurring mutation found in four different south Asian haplogroups: M3c, M5a1a, M32, and M51 [3, 8, 9]. With the observed ATPase6 gene substitutions, cases and controls sorted into their proper mtDNA haplogroups (Table 1), we can see that of the mutations in the 20 POI study cases, 7 cases are belong to haplogroup U7, 5 individuals belong to U2b1 and B4a, and one each to haplogroups M4b2 and M39. In the control group only two participants had common haplogroup mutations and they belong to haplogroups M4b2 and B4a. This extreme difference in haplogroup distribution demonstrates clearly that the controls and POI cases were recruited from significantly different hereditary populations. Association studies produce spurious results if the cases subjects are not matched properly with control subjects [10]. It is apparent that the results in this study, for example, were misinterpreted by their authors and that the control group was not a scientifically relevant control. Once again we demonstrate the importance of examining mitochondrial mutations against the backdrop of known haplogroups, and the importance of using phylogenetic in studies of human disease. Failing to employ all data relevant to mitochondrial studies often presents a false picture of disease association, leading to incorrect conclusions and potentially inefficient and faulty new diagnostic tests. M. G. Palanichamy (&) Y.-P. Zhang Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming 650 091, Yunnan, China e-mail: empalani@yahoo.com