Warfarin resistance in Rattus losea in Guangdong Province, China

Control of rodent populations is performed worldwide with coumarin derivatives, such as warfarin. After widespread use, their effect has been diminished by the rapid spread of resistant rodents. Warfarin resistance in Rattus loseas in Jiangmen and Zhanjiang City, Guangdong Province, was investigated by lethal feeding tests. Twenty-three of 30 R. loseas trapped in Jiangmen City were assayed as warfarin-resistant individuals, whereas only 1 of 30 rodents in Zhanjiang was resistant. These results emphasize the need for thorough resistance monitoring as a basis for adequate control measures to prevent the use of ineffective rodenticides in Jiangmen City. The resistance mechanism mainly involves VKORC1, the molecular target for coumarin drugs. VKORC1 mRNA expression in wild-caught resistant animals showed no difference compared with that in susceptible individuals. Mutation screening of VKORC1 was carried out and an Arg58Gly mutation was identified as the prevailing type in R. loseas from Jiangmen City, which may constitute the genetic basis of anticoagulation resistance in R. losea in this resistance region.     

Vitamin K requirement and reproduction in bromadiolone-resistant Norway rats

BACKGROUND: Nucleotide polymorphisms in the VKORC1 gene can be linked to anticoagulant rodenticide resistance in Norway rats (Rattus norvegicus Berkenhout). This provides a fitness advantage to rats exposed to anticoagulant actives, but may also cause fitness costs. The vitamin K requirement and reproductive parameters of bromadiolone‐resistant rats (Westphalian resistant strain; VKOR variant Tyr139Cys) and bromadiolone‐susceptible Norway rats were compared. RESULTS: At vitamin K deficiency, blood clotting times increased in all homozygous resistant males within 8 days and in 80% of homozygous resistant females within 15 days. There was little effect on blood clotting in heterozygous males and no effect in heterozygous females and VKOR wild‐type individuals. Litter size was about 20% higher in sensitive pairs compared with resistant pairs. Testes growth, male gonad weight, sperm motility and testis cell concentration were unaffected by the mutation. CONCLUSIONS: The VKOR variant Tyr139Cys causes considerable physiological cost in Norway rats in terms of vitamin K requirement and reproduction. This may affect the distribution and spread of resistant individuals in the wild. Decreased litter size of resistant parents seems to be due to lowered female reproductive performance, as there was no significant effect of the mutation on any aspects of male reproduction considered, but this requires further study. Copyright © 2011 Society of Chemical Industry     

Comparison of the inhibition effect of different anticoagulants on vitamin K epoxide reductase activity from warfarin-susceptible and resistant rat

Anti-vitamin K drugs are widely used as anticoagulant in human thromboembolic diseases. Similar compounds have also been used as rodenticides to control rodent population since 1950s. Massive use of first generation anticoagulants, especially warfarin, has lead to the development of genetic resistances in rodents. Similar resistances have been reported in human. In both cases, polymorphisms in VKORC1 (Vitamin K epoxide reductase subunit 1), the subunit 1 of the VKOR (Vitamin K epoxide reductase) complex, were involved. In rats (Rattus norvegicus), the Y139F mutation confers a high degree of resistance to warfarin. Little is known about the in vitro consequences of Y139F mutation on inhibitory effect of different anticoagulants available. A warfarin-susceptible and a warfarin-resistant Y139F strain of wild rats (Rattus norvegicus) are maintained in enclosures of the Lyon College of Veterinary Medicine (France). Using liver microsomes from susceptible or resistant rats, we studied inhibition parameters by warfarin (K_i = 0.72 ± 0.1 μM; 29 ± 4.1 μM), chlorophacinone (K_i = 0.08 ± 0.01 μM; 1.6 ± 0.1 μM), diphacinone (K_i = 0.07 ± 0.01 μM; 5.0 ± 0.8 μM), coumachlor (K_i = 0.12 ± 0.02 μM; 1.9 ± 0.2 μM), coumatetralyl (K_i = 0.13 ± 0.02 μM; 3.1 ± 0.4 μM), difenacoum (K_i = 0.07 ± 0.01 μM; 0.26 ± 0.02 μM), bromadiolone (K_i = 0.13 ± 0.02 μM; 0.91 ± 0.07 μM), and brodifacoum (K_i = 0.04 ± 0.01 μM; 0.09 ± 0.01 μM) on VKOR activity. Analysis of the results leads us to highlight different anticoagulant structural elements, which influence inhibition parameters in both susceptible and Y139F resistant rats.     

The influence of anticoagulant resistance on effective rodent control in the UK1

Widespread use of warfarin, and other multiple-dose anticoagulants, selected populations of warfarin-resistant rodents in the UK and in other countries. The effectiveness of rodent control was dramatically reduced when the resistant animals formed a large proportion of a population. The second-generation anticoagulants were developed to overcome these practical control problems with warfarin and were considered to be effective rodenticides against warfarin-resistant populations. In the UK, however, difenacoum showed reduced efficacy for controlling an established warfarin-resistant Rattus norvegicus population covering a substantial area of farmland in southern England. Continued use of difenacoum selected for difenacoum-resistant animals, so that the rodenticide is now ineffective for controlling rats in three counties. Brodifacoum was subsequently used to control some infestations and there is evidence that these treatments selected for animals with an increased level of resistance to brodifacoum. Anticoagulant resistance in Mus domesticus is less of a practical problem because of the availability of non-anticoagulant rodenticides for the control of this species. There is evidence, however, of bromadiolone resistance in M. domesticus trapped on farms in the UK. Recent investigations of the mechanism of anticoagulant resistance in R. norvegicus have indicated that vitamin K3 (menadione) is an antidote to anticoagulants in resistant animals. This form of the vitamin is included as a dietary supplement in poultry and pig food and would aid the survival, and therefore increase the selection, of resistant animals when anticoagulants are used exclusively.     

A review of biochemical mechanisms of warfarin resistance in the house mouse

The biochemical mechanisms of warfarin resistance in the house mouse (Mus musculus L.) have not been fully investigated. In some populations of warfarin-resistant mice there is a reduction in sensitivity of hepatic vitamin K-epoxide reductase to inhibition by warfarin. This is similar to a proposed mechanism of anticoagulant resistance in the Norway rat (Rattus norvegicus Berk.). The same enzyme in other warfarin-resistant populations is, however, sensitive to warfarin inhibition. Other studies have indicated that detoxification may play a role in conferring warfarin resistance in house mice.     

Revised methodology for a blood-clotting response test for identification of warfarin-resistant Norway rats (Rattus norvegicus)

A blood-clotting response test for warfarin resistance in Norway rats ( Rattus norvegicus ) was developed by our laboratory in the late 1970s, based on knowledge of biochemical mechanisms available at that time. That test used warfarin, its the free base which is not watersoluble, and vitamin K₁ 2,3-epoxide as an antidote for warfarin-resistant rats only. We have modified the above test to use a water-soluble salt of vitamin K₃ (1 mg kgg⁻¹ body weight), which is an antidote in a wider range of warfarin-resistant rat strains than vitamin K₁ 2,3- epoxide, and a water-soluble salt of warfarin (5.4 mg kg⁻¹ body weight). Sodium warfarin and vitamin K₃ are administered by oral gavage, and the blood-clotting response measured 24 h later. In a series of validation tests there were no significant differences between results obtained by either method. The new method, however, uses materials which are commercially available, and eliminates the possibility of misclassifying warfarin-resistant rats as susceptible because vitamin K₁ 2,3-epoxide was not an antidote in those strains. We also present evidence that measuring blood-clotting response to feeding on a vitamin K-free diet for 4 days is not a reliable method for determining the genotype of warfarin-resistant rats.     

Laboratory and field trials of the rodenticide brodifacoum against warfarin-resistant Norway rats

Norway rats (Rattus norvegicus) trapped in a low-income housing area in Raleigh, North Carolina, and on a poultry farm in Garner, North Carolina, manifested high levels of resistance to warfarin in laboratory tests. Of the rats tested, 59.1 and 91.7% from the Raleigh and Garner trap sites, respectively, survived a 6-day no-choice test of a diet containing 0.005 % warfarin. The warfarin-resistant rats were subsequently given a choice of a 0.005% brodifacoum bait and a placebo diet. Of 27 rats, 19 died after a 3-day test. Survivors had consumed significantly less brodifacoum (0.1 < P > 0.05) than those that died, but the survivors also died when subjected to an additional 1-day no-choice test of the brodifacoum bait. Field trials, in which warfarin-resistant rats in four poultry houses were fed with poison bait for 14–16 days with 0.005% brodifacoum in a pelletised bait (‘Talon’), resulted in 87–99 % control being achieved.     

Warfarin-based rodenticides: Mode of action and mechanism of resistance

Warfarin and related substances have been in use as rodenticides for fifty years. They act by binding to the enzyme vitamin K 2,3-epoxide reductase, thereby interrupting the cellular recycling of vitamin K. Vitamin K in its hydroquinone form is an essential cofactor for the synthesis of functional prothrombin and related blood-clotting factors. The binding with the reductase is essentially irreversible, indicating these compounds have a prolonged half-life in target tissues; 7–10 days for warfarin and congeners and over 100 days for the second generation rodenticides or ‘superwarfarins’ such as difenacoum, brodi-facoum, and flocoumafen. Rat liver contains 1–2 nmole of enzyme per gram tissue which is a 4–5 fold overcapacity for maintaining effective vitamin K recycling. The use of warfarin as a rat poison has resulted in the natural selection of warfarin-resistant rats. The resistance is inheritable. Two distinct warfarin resistance genotypes, Welsh and Scottish, have been identified, clearly differing in their biochemistry of vitamin K epoxide reductase. In the Welsh strain, resistance arises from an altered enzyme expressing reduced reactivity to warfarin, whereas the reductase from the Scottish strain is as sensitive as the normal enzyme, but the interaction with warfarin is now readily reversible. The altered enzyme leaves the Welsh rat in need of higher dietary vitamin K intake. The superwarfarins cope with the resistance by having their structures firmly bind with the altered enzymes. Reduced sensitivity to warfarin-based rodenticides may also be pharmacokin-etically based, arising from increased warfarin biotransformation. This mechanism may be responsible for resistance to some of the superwarfarins such as difenacoum. A third resistance mechanism may arise from an enhanced capacity to synthesize vitamin K from menadione, a commonly used additive in animal foods on farms. The choice of rodenticide in the case of warfarin resistance should be guided by the underlying mechanism of resistance.     

Resistance tests and field trials with bromadiolone for the control of Norway rats (Rattus norvegicus) on farms in Westphalia, Germany

BACKGROUND: The aim of this study was to determine the incidence and the level of resistance to bromadiolone among rats on farms suspected of being foci of resistance by using the international normalised ratio (INR)‐based blood clotting response (BCR) test. Whether the level of reduced susceptibility constitutes ‘practical resistance’ was subsequently determined in field trials. RESULTS: The 2.5 multiple of the ED₅₀ baseline was used to test for the incidence of resistance, and higher multiples in the range of the suspected resistance factor were used to investigate the degree of resistance. The ED₅₀ values of bromadiolone in resistant rats were confirmed in the range 4.70–7.05 mg kg^?1 for males and 4.62–6.61 mg kg^?1 for females. Variations within these ranges appeared between farms. According to the BCR resistance tests, 50–100% of rats were classified as resistant prior to the field trials; 29–100% of rats survived the treatments. CONCLUSION: BCR tests based on the use of the INR and baselines are suitable for determining the incidence and for assessing the level of resistance in populations of Norway rats. The majority of rats of the Westphalian resistant strain, characterised by the Y139C marker in VKOR, are resistant to bromadiolone under practical control conditions. Copyright © 2011 Society of Chemical Industry     

Molecular and biochemical mechanisms of organophosphate resistance in laboratory-selected lines of the oriental fruit fly (Bactrocera dorsalis)

Genetic and biochemical factors leading to resistance to various organophosphate (OP) based insecticides were studied in lines selected for OP-resistance in the oriental fruit fly Bactrocera dorsalis. Lines were separately selected for resistance to naled, trichlorfon, fenitrothion, fenthion, formothion, and malathion. Overall, these lines showed increased resistance ratios ranging from 13.7- to 814-fold relative to a susceptible (S) line. Also, in these newly selected lines the same three point mutations in the ace gene, previously identified in resistance studies and designated as I214V, G488S and Q643R, were found. As expected, the enzyme from the resistant lines showed lower overall activity and reduced sensitivity to inhibition by fenitrothion, methyl-paraoxon and paraoxon compared to the wild type acetylcholinesterase (AChE) enzyme. The apparent V_max values for esterase from the resistant lines were 1.2-3.69 times higher than that of the S line. Although only the naled-, trichlorfon- and fenthion-r lines showed lower esterase affinities (based on apparent K_m values) compared with the S line, all of the V_max/K_m ratios were higher in the resistant lines compared to that of the S line. The OP-resistant lines also displayed an overall similar pattern of isozyme expression, except for one additional band found only in the naled-r line and one band that was absent in the trichlorfon-, malathion-, and fenthion-r lines. Our results also show that overall, multiple examples of high OP resistance in selected lines of B. dorsalis exhibiting the same genetic alterations in the ace gene seen previously resulted in different effects on esterase enzyme activity in relation to various OP compounds.     

Distribution and frequency of VKORC1 sequence variants conferring resistance to anticoagulants in Mus musculus

BACKGROUND: Emerging resistance to anticoagulant rodenticides may significantly impair house mouse (Mus musculus L.) control. As in humans and rats, sequence variants in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) of house mice are strongly implicated in the responses of mice to anticoagulants. This study gives a first overview of the distribution and frequency of such potentially resistance‐conferring sequence variants in house mice, based on tissue samples from 30 populations in Germany, Switzerland and the Azores. RESULTS: Except for one population from south Germany, sequence variants were found in individuals from all locations sampled (29 out of 30 sites surveyed), with less than 10% of the individuals matching the wild‐type genotype. The most frequent and widespread amino acid substitutions were Leu128Ser, Tyr139Cys and a group of linked sequence changes (Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu). Where these substitutions occurred as the sole variant, the proportion of homozygous individuals was 72–83%. CONCLUSIONS: An evaluation of published data revealed that the three most frequently found sequence variants are associated with a substantial loss of rodenticide efficacy of first‐generation anticoagulants (e.g. warfarin, coumatetralyl), as well as the second‐generation compound bromadiolone and most probably also difenacoum. Knowledge of the distribution and frequency of resistance‐conferring sequence variants will stimulate their further functional characterisation and facilitate the choice of effective active substances for house mouse control. Copyright © 2011 Society of Chemical Industry     

Anticoagulant resistance: a relevant issue in sewer rat (Rattus norvegicus) control?

BACKGROUND: The majority of rat problems in cities are thought to be related to defective sewers, and the use of anticoagulant rodenticides in such places is often implemented as part of regular urban rodent control. Knowledge pertaining to the resistance status of sewer rat populations is non‐existent, which may be leading to control problems in cities. It has become crucial to provide knowledge on the prevalence of resistance and how different control strategies have affected its prevalence among sewer rat populations. The prevalence of resistance was investigated in six sewer locations in Copenhagen and its suburban area by means of the blood clotting response (BCR) test and amplification refractory mutation system polymerase chain reaction (ARMS PCR) analysis, and by additional sequencing of the VKORC1 gene. The sewer locations were chosen to represent three different control strategies: (i) no anticoagulant use for approximately 20 years; (ii) no anticoagulant use for the last 5 years; (iii) continuous use for several decades up to the present. RESULTS: A low level of anticoagulant resistance was found in the sewers regardless of control strategy. Surprisingly, none of the rats, including the resistant rats, had resistance‐related mutations in the VKORC1 gene. CONCLUSION: The results of this study suggest that the genetic background of anticoagulant resistance may have to be redefined in respect of resistance‐related changes in the VKORC1 gene. Copyright © 2009 Society of Chemical Industry     

普通小麦-柔软滨麦草易位系M97抗条锈基因的遗传分析和分子作图

为了明确M97抗条锈性遗传规律,在苗期用7个小麦条锈菌系对M97与感病品种铭贤169的杂交后代F1、F2、F3和BC1代进行抗条锈性遗传分析,并对M97抗Sun11-4的抗条锈基因进行SSR分子标记。M97对Sun11-4和Sun11-11的抗病性均由1对显性基因控制,对CY29、CY30、CY33的抗病性由1显1隐2对基因共同控制,对CY31的抗病性由2对显性基因独立或重叠作用控制。以接种Sun11-4的F2代分离群体构建作图群体,筛选到Xwmc222、Xwmc147、Xbarc229和Xwmc339等4个与抗病基因连锁的SSR标记,其遗传距离分别为3.4、4.8、7.6和12.1 cM。将该抗病基因定位于小麦1DS染色体,且该基因不同于已知的抗条锈基因,暂命名为YrM97。用YrM97两侧遗传距离最近的2个标记Xwmc222和Xwmc147对42个黄淮麦区主栽小麦品种进行分子检测,仅有9.5%的品种具有与YrM97相同的标记位点。     

Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus)

Resistance to warfarin has been connected to an increase in dietary requirement for vitamin K in British strains of the Norway rat, Rattus norvegicus (Berk). This study examines vitamin K requirement of Danish anticoagulant-resistant Norway rats using a vitamin K deficient feeding test. Wild bromadiolone-resistant rats sampled from different localities in Denmark and rats from bromadiolone-resistant and susceptible laboratory strains were fed on a vitamin K deficient diet over a maximum period of 15 days. Development of vitamin K deficiency, measured as reduced blood-clotting capacity, took place in 43% of the Danish resistant rats and was independent of sex, treatment with supplementary vitamin K3 and sampling locality. Development of deficiency was slower for resistant rats that were supplemented with vitamin K3 prior to the feeding test, suggesting storage of the vitamin K in a vitamin body pool. Intraperitoneal administration of vitamin K1 revealed that 80 microg vitamin K1 kg(-1) bodyweight was sufficient to restore normal blood clotting activity in deficient rats, while 60 microg vitamin K1 kg(-1) bodyweight was insufficient. We conclude that vitamin K requirement is moderately increased in Danish homozygous resistant rats whereas heterozygous resistant rats only have a minor increase in vitamin K requirement compared with susceptible rats. We found no indication of different resistance types being present in our test material since vitamin K requirement was not different between rats from separate sampling localities.     

Resistance to anticoagulant rodenticides in Germany and future strategies to control Rattus norvegicus

Widespread anticoagulant resistance was discovered in populations of the brown rat (Rattus norvegicus Berk.) in an area of roughly 8000 km² in north-west Germany. Resistance testing was performed by feeding tests and/or by measuring blood clotting response after intraperitoneal injection of a sublethal testing solution. A hierarchical resistance system was found with warfarin resistance at the base followed by bromadiolone/coumatetralyl resistance to difenacoum resistance at the top. Warfarin resistance was spread over the whole area with reduced incidence towards the edges. Difenacoum resistance represented the highest level found so far and was restricted to the inner zone of the resistance area where it occurred with a frequency of 6% of all individuals tested. Breeding experiments with bromadiolone-resistant rats showed that expression of the bromadiolone resistance gene differed in the two sexes, suggesting additional sex-linked modifying effects to the resistance gene. Control strategy within the resistance area with respect to prevention of further selection for resistance is discussed.     

Resistance to azoxystrobin in Alternaria isolates from pistachio in California

Failure to control Alternaria late blight in a few California pistachio orchards was observed after only 3-4 years of consecutive applications of azoxystrobin-based fungicide programs. A total of 72 isolates of Alternaria alternata, Alternaria tenuissima, and Alternaria arborescens, the causal organisms of Alternaria late blight, were collected from pistachio orchards with (58 isolates) and without (14 isolates) a prior history of azoxystrobin applications. The sensitivity to azoxystrobin was determined in conidial germination assays. Isolates from orchards with a history of azoxystrobin applications had EC₅₀ values greater than 100 μg/ml, whereas isolates from orchards without a prior history of azoxystrobin usage had EC₅₀ values ranging from 0.008 to 0.045 μg/ml. Azoxystrobin resistance correlated with a single mutation in the cytochrome b (cyt b) gene causing a change of glycine to alanine at amino acid position 143. A pair of PCR primers AF and AR was developed that amplified a 226-bp DNA fragment of the cyt b gene containing the mutation site from all three Alternaria species but not from 30 other fungal species frequently found on pistachio. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzyme Fnu4HI allowed differentiation of the PCR fragment of wild type cyt b gene from that of mutated gene. This method will aid in a fast detection of azoxystrobin resistance in these three Alternaria species.     

Distribution of VKORC1 single nucleotide polymorphism in wild Rattus norvegicus in France

BACKGROUND: Anticoagulant rodenticides are commonly used to control rodent pests all over the world. These pesticides inhibit one enzyme of the vitamin K cycle, Vkorc1, and thus prevent blood clotting and cause death by haemorrhage. Resistance to anticoagulants was first observed in Scotland in 1958, and more potent anticoagulants have been developed to overcome this obstacle. Unfortunately, these chemicals are very toxic and cannot be used everywhere. Some authors have shown that resistance to anticoagulants seems closely linked with single nucleotide polymorphism (SNP) in the Vkorc1 gene. RESULTS: This study draws a map of SNP and haplotypes found in Vkorc1 in rats from different areas of France. Some of them had never been described before. Moreover, the Y139F mutation, described previously in France and Belgium, is the most frequent in France. This mutation is known to be associated with a strong resistance to anticoagulants, and it was found in 28% of the samples. CONCLUSION: This biomolecular approach to studying and detecting resistance is easier to carry out than the phenotypic approach measuring blood coagulation time because it can be conducted on biological samples from dead animals, and it is less dangerous for the operator. Copyright © 2009 Society of Chemical Industry     

大豆对灰斑病菌15号小种的抗病基因定位及标记检测

为明确大豆对灰斑病菌15号小种的抗性位点,以大豆抗病品种垦丰16、感病品种绥农10及其杂交F₂、F₃代群体为试验材料,在接种鉴定的基础上,运用SSR标记技术及分离群体组群分析法(BSA法)对垦丰16抗病基因进行了定位,并应用108份大豆新品系对标记进行了符合性检测。结果表明,垦丰16对15号小种的抗性受1对显性基因控制,抗病基因位于大豆染色体组的J连锁群上,将该基因定名为Rcs15。用Mapmaker/Exp 3.0 b进行连锁分析,获得了5个与抗病基因紧密连锁的SSR标记:Satt 529、Satt 431、Sat_151、Satt 547和Sat_224,标记与抗病基因间的排列顺序和遗传距离为Sat_151-10.7 cM-Satt 529-18.5 cM- Rcs15-6.7 cM-Satt 547-7.8 cM-Sat_224-10.7 cM-Satt 431。标记符合性检测结果显示,Satt 547和Sat_224的检测准确率达到85%以上,可用于分子标记辅助选择育种和抗源筛选。     

增强型绿色荧光蛋白基因转化大豆疫霉菌及其表达

为了探讨大豆疫霉菌Phytophthora sojae的侵染过程及其在土壤中的生态学,采用CaCl2-PEG介导的原生质体转化方法,将外源增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)基因转化到大豆疫霉菌中,观察EGFP基因在大豆疫霉菌不同生育时期的表达,对转化子中的EG-FP基因进行PCR检测,并对转化子的生长、发育及致病性进行测定。结果显示,EGFP基因能够在大豆疫霉菌菌丝、游动孢子囊和卵孢子中稳定表达,并在475 nm蓝光激发下发出绿色荧光;转化子的菌丝生长速率与野生型无显著差异,个别转化子在无性繁殖和有性生殖方面与野生型有显著或极显著差异,其中一个转化子的致病型发生了改变。研究表明获得的EGFP基因转化子可以作为研究大豆疫霉菌侵染及定殖的材料。     

三个小麦-簇毛麦易位系抗条锈性遗传及基因间关系分析

采用8个我国当前流行的条锈菌生理小种(菌系)对三个易位系进行抗锈性评价,并用CYR30、CYR31、Su-4和单孢菌系CYR32-6对三个易位系与感病品种铭贤169配制的F1、BC,1F1和F2代株系以及三个易位系之间双列杂交的F2株系进行遗传分析和等位性分析.结果表明:三个易位系是优秀的小麦抗条锈病资源;V9128-1对CYR30、CYR32-6和Su-4的抗病性由1对显性基因控制,对CYR31的抗病性由1显1隐2对基因独立控制,V9128-3对四个菌系的抗病性均由1对显性基因控制,V3对CYR32-6和Su-4的抗病性均由2对显性基因互补作用控制,对CYR31的抗病性由1显1隐2对基因独立控制或由1对显性基因控制;V9128-1与V9128-3对CYR31、CYR32-6和Su-4有相同或紧密连锁的抗病基因,且对CYR30、CYR32-6和Su-4的抗病基因与V3都不同.但与V3含有相同或紧密连锁的抗CYR31基因.